NANOCULTURE
Delivered to
The
March 1, 1999
Copyright 1999 by William H. Beauman
The
research for this paper led me to reread one of my all-time favorite science
fiction novels, Macroscope, by Piers Anthony. It was set in the
not-too-distant future after a group of super-children, endowed by genetic
engineering with the most enhanced and idealized genomes imaginable, reached
adulthood and began their life's work. There were a couple hundred of them, and
they were reared together in a research community by professional
"parents." They were all of mixed race (that is, literally mixed in
the test tube-all should benefit from "hybrid vigor," a genetic
attribute that is the opposite of "inbred weakness") ("We're considered
non-white," one of them told a new acquaintance), and all had
non-gender-identified names such as Spruce or Agate. One of the surprises that
emerged from the great experiment as the children grew up was that there were
not nearly as many super-geniuses as expected, considering the efforts that had
been expended in that direction. In fact, many of them seemed to be downright
ordinary, and they were a disappointment to their creators.
But there certainly were some super-geniuses, and the star of the group,
Brad, had invented the Macroscope, a super-telescope mounted in a space station
that could produce views of planets in distant galaxies as distinct and
detailed as if one were simply looking out the window. The story began with one
of the "ordinary" super-children, Ivo, a "reject" who had
been bounced back into the ordinary world, making his way from rural
"Glooms
of the live-oak, beautiful-braided and woven
With intricate shades of the vines that myriad-cloven
Clamber the forks of the multiform boughs,--
Emerald twilights,--
Virginal shy lights,
Wrought of the leaves to allure to the whisper of vows,
When lovers pace timidly down through the green colonnades
Of the dim sweet woods, of the dear dark woods,
Of the heavenly woods and glades,
That run to the radiant marginal sand-beach within
The wide sea-marshes of Glynn;--"
Oh,
what gorgeous language! Of course, this immediately endeared the book to me,
but it is the science described in Macroscope that makes it a great
sci-fi story.
The call for help that Ivo was answering was for his famous brother, the
Macroscope inventor. In their survey of the universe with their new toy, the
scientists had encountered a sort of galactic encyclopedia being broadcast into
space. It was a fabulous opportunity to learn, but the broadcast was protected
by a "mental trap" program that burned out people's minds whenever
they tried to tap into it. It was based on seductive logic, so that the smarter
one was, the more easily one was ensnared. Of course, the geniuses were the
first to go, starting with the super-genius who started it all. Poor Brad had
been turned into a vege-table, and it was hoped that Ivo, his closest childhood
friend, might be some help. While Ivo was on the Macroscope space station there
was political unrest there and on Earth, leading to an insurrection of the
scientists, and ending in a bizarre chess tournament with the Macroscope itself
as the prize. Ivo's real genius turned out to be chess, so he won, and the
other scientists helped him and a small group of friends "liberate"
the Macroscope, to keep it from the politicians and generals, and they started
off on the most fantastic picaresque adventure story I have ever read.
One of their number-a "lowly housewife" with no scientific
training-was able to get past the mind-numbing guard program and copy detailed
instructions for the assembly of extraordinary machines-nano-technology. She
and her husband, an engineer, spent a full year building the first machine, and
another year for the next two, but after that, those machines made other
machines and so on that could do nearly anything, from sealing a leaking window
to terraforming a dead planet. But first came the months of tedious
micro-manipulation to build tiny circuits and engines on an atomic scale.
We have been doing that in the real world for about a decade now. It started
when IBM scientists reproduced their company's logo in individual silicon
atoms, manually pushed into place with a scanning, tunneling atomic force
microscope operating in reverse. The atomic force microscope is completely
different from any light microscope or electron microscope, because it does not
focus anything. It is almost entirely mechanical. Think of a tiny record
turntable with a tone arm ending in a needle attached to a flexible beam
cantilevered from the tip. Remember how delicately one had to lower the needle
onto the record, and how the tone arm had to be perfectly counter-balanced, to keep
the pressure of the needle very lightly in the groove. The atomic force
microscope is very much like that, except that, instead of a diamond-tipped
needle at the end, there is a long, tapering electrode made of pure silicon or
a metal, drawn out to the ultimate thinness-a tip with a diameter of only a few
atoms. When it is electri-fied, the charge on the tip can sense the electrical
field of individual atoms. The tip is played back and forth across the flat
surface of a perfect crystal, much like a phonograph needle that eventually
traverses the entire surface of a record, and wherever there is a
"bump"-an atom sticking up above the others-the electro-magnetic
signal is recorded. Thus have the shapes of single molecules been confirmed.
Operating in reverse, the electrified tip is used to nudge atoms here and
there, one at a time, at will. It is crude and awkward now, analogous to
nudging individual grains of sand with a telephone pole sharpened to a
pencil-point, but hardly a week goes by without the announcement of another
advance in the fabrication of molecular wires, tubes, even motors on the
nano-scale.
"Nano-" is a prefix meaning "one-billionth," and a
nanometer (nm) is the size of individual, small molecules. Just one more power
of ten smaller brings us to Angstroms, the size of single atoms. Until the
present decade, the smallest features that could be made in manufactured
objects such as computer chips were about one-quarter of a micron, or 250 nm in
size. Then came the discovery of buckminsterfullerenes, a new form of pure
carbon found in the soot from carbon arcs, named after the inventor of geodesic
domes, which they resemble. The smallest fullerene, or "buckyball,"
as they are affectionately called, is C60, a sphere of carbon atoms arranged in
the pattern seen on a soccer ball. It has a diameter of 30 nm, but there is a
whole family of them, and they nest one inside another like Russian dolls or
the layers of an onion. It is also possible to make hemispheres and long
fullerene nano-tubes with diameters from less than 2 to more than 200 nm and
lengths up to 5,000 nm or 5 microns, all of which nest together readily. They
are the strongest fibers known, and some believe they are the strongest fibers
of any kind that are theoretically possible to make. The balls and tubes can be
filled with metals, creating tiny wires and other structures that can be used
to build things.
All this is the realm of physicists, but now, here come the chemists. They have
discovered that one can use solutions of metals like silver nitrate or gold
chloride, let the metal ions adsorb onto the surface of dissolved polymers, and
then chemically reduce them to the metallic form as a coating on the outer
surface of the polymer molecules. And it turns out that the polymers that are
easiest to control are biopolymers such as the myosin protein in muscle fibers,
and especially DNA molecules. Thus, one can make a gold wire the length and
diameter of the microfibrils inside individual cells, like those of the
"spindle" that orients the chromosomes in the center and then pulls
them toward opposite poles during cell division.
Finally, biochemists and molecular biologists are getting into the picture by
having living cells do the fabrication for them. It turns out that the best
molecular motor has already been made by Mother Nature: the biochemical motors
that make cilia move, and which power sperm on their epic quest. Each molecular
motor is comprised of three pairs of protein molecules arranged in the shape of
a hexagon, with a seventh molecule protruding from the center like an axle
attached to a wheel. A young post-doc from the University of Tokyo showed just
last year that each pair of base proteins causes the "axle" protein
to rotate one-third of a circle, or 120 degrees, when powered by one molecule
of adenosine tri-phosphate, or ATP, the energy "currency" of living
cells. Best of all, the protein motor operates with nearly 100% efficiency, and
the whole apparatus is only about 10 nm in diameter. Now there's a motor one could
do something with!
This biological connection is one that Piers Anthony failed to predict in Macroscope.
Maybe somebody will eventually succeed in making nano-machines the hard way,
with physical mechanics, but it is clear to me that "nanoculture" in
the test tubes and flasks of molecular biology laboratories will take the big
steps much more quickly.
This thought has occurred to the barons of commerce, too. Two extra-ordinary
global business trends have begun to take shape in just this decade. The first
one involves the Human Genome Project, which is the gargantuan, international
effort to map out the entire two-billion DNA base-pair sequence of the
100,000-gene complement of all 23 human chromosomes-the "Book of
Man." The official effort is headed by Dr. James Watson of the Watson
Crick team that first determined the chemical nature and structure of DNA.
Watson's group has been at it for about five years already and has completed
nearly half of the job. The idea was that there would be only one human genome
project, every-one would share the information openly, and there would be no
patenting of special genes or sequences. That ideal lasted for only a very
short time, when first one, then another, then a third commercial group
announced plans to do it on their own-faster and cheaper than the government's
plan. Now at least half a dozen research groups, from
"To
the edge of the wood I am drawn, I am drawn,
Where the gray beach glimmering runs, as a belt of the dawn,
For a mete and a mark
To the forest dark:--
So:
Affable live-oak, leaning low,--
Thus-with your favor-soft, with a reverent hand,
(Not lightly touching your person, Lord of the land!)
Bending your beauty aside, with a step I stand
On the firm-packed sand,
Free
By a world of marsh that borders a world of sea.
Sinuous southward and sinuous northward the shimmering band
Of the sand-beach fastens the fringe of the marsh to the folds of the land.
Inward and outward to northward and southward the beachlines linger
and curl
As a silver-wrought garment that clings to and follows the firm sweet limbs
of a girl.
Vanishing, swerving, evermore curving again into sight,
Softly the sand-beach wavers away to a dim gray looping of light."
I
suppose there is no hope of ever getting the great, greedy chemical and
pharmaceutical companies to exhibit a similar reverence for nature
The other new global business trend is nothing less than the wholesale
restructuring of the entire chemical industry. One after another, the behemoth,
multi-national chemical companies are getting rid of their core businesses and
buying into the biotechnology industries. Imperial Chemical Industries (ICI)
started it all in 1993, when it split off its huge petroleum holdings and
merged operations to form the biochemical specialty firm, Zeneca. Now ICI is
all agri-cultural chemicals and pharmaceuticals. Shortly thereafter, Ciba-Geigy
and Sandoz both sold their standard chemical businesses to specialty companies
and combined the remainder to form the giant life sciences corporation,
Novartis, with $13 billion invested in health care, $6 billion in agribusiness
and $3 billion in nutrition business. Starting two years ago, Monsanto shed its
basic chemicals and bought $6.5 billion worth of agricultural biotechnology
expertise. Now, Hoechst and Rhone-Poulenc have both dumped their core chemical
businesses and invested $12 billion and $7 billion, respectively, into drugs
and agribusiness companies. And DuPont, after buying a huge petroleum producer
even larger than themselves, has just gotten rid of it and spent $6 billion to
enhance its life sciences portfolio. Of all the world's giant chemical companies,
only Dow, Bayer and BASF have retained their core chemical businesses and
moderated their biotechnology acquisitions somewhat. Jurgen Dormann, Hoechst's
chairman, explained it this way: "Concentrating on life sciences means a
shift from cyclical, high-volume, low-margin products to stable, low-volume,
high margin products and from a high asset base and low R&D investment to a
small asset base and high R&D investment-in other words, from bricks to
brains." Gary Pfeiffer, Chief Financial Officer at DuPont, says he
considers the present potential in the life sciences to be greater than that of
polymer chemistry when that discipline was young nearly a century ago. Wow! I
wonder what the next "Nylon" will be?
And what do these two trends mean? They mean the world of commerce is changing
fundamentally. The dozen or so biotechnology companies that started up on their
own in the previous decade have been gobbled up, even though most of them have
yet to show a profit, just because of the head start their expertise promises
to whoever owns them. And what promise! Genetic engineering and biotechnology
will revolutionize agriculture, materials science, pharmaceuticals, and, most
of all, medicine. Already, "pharmaceuticals" is being spelled with an
"f", and "farming" is being spelled with a "ph."
Human insulin is already being produced by "pharm" animals, and the
vaccine for hepatitis B comes from bacterial cultures. Before long, people will
get vaccinations against the rota-viruses in polluted water, which cause infant
diarrhea and kill more people than any other disease, simply by eating a
genetically engineered potato or apple. Milk from genetically engineered cows
will carry antibodies against several diseases at once. Critical food crops are
already being bio-engineered to produce their own insecticides. I don't mean
dangerously toxic synthetic pesti-cides like DDT, but bio-toxins such as that
produced by Bacillus thuringiensis, or "BT" bacteria, which
protects all sorts of crops, from tomatoes to cotton to spruce trees, but is
harmless to all creatures like us with a backbone. Now, rather than having to
spray the crops with the bacterial culture, the bacterial gene that codes for
the toxin is simply inserted into the genome of the crop, so that the cotton
plants make their own BT toxin. There is already a third-world back-lash
against the agrochemical companies and their tactic of genetically sabotaging
the protected crops' seed production, so that everybody has to buy new seeds
every year. They don't miss a trick, do they-it may be heartless, but it is
good business.
As important as the bio-technology nanoculture will be for agriculture, I
believe its effects on human genetics and human medicine will affect the lives
of our friends and families even more. Let's talk about genetics first. Dean
Hamer, the scientist at the National Institutes of Health in Bethesda, MD, who
wrote a book on the locus of the "gay gene" on the X-chromosome a few
years ago, published a fascinating book last year, Living With Our Genes,
in which he explains "why they matter more than you think." It is now
certain that genes determine much more than physical structures-they govern
feelings, attitudes, preferences in a most fundamental way. Whether one is shy
or outgoing, glum or happy with life, a risk-taker who jumps off bridges with a
Bungee cord attached or one who curls up with a book, whether or not one angers
easily or succumbs to addiction, all are genetically determined. My favorite
example of the genetic imperative is the story of two identical twin boys
separated at birth. Thirty years later, they met for the first time and were
amazed to find how similar their lives were. They resembled each other, of
course, but they also had similar haircuts and mustaches, and both preferred
the color blue. They had similar jobs-one drove a fire-truck; the other drove
an ambulance. They had nearly identical cars-big 4-wheel-drive, off-road
monsters (blue, of course) with oversize tires. Both had big dogs, the same
arsenal of guns, the same penchant for hunting. Both even had diminutive,
strawberry-blonde wives named Marge! Well, sure, some of that has to be
coincidence .
It is already possible for couples to cull through several embryos at an in
vitro fertilization clinic and select the one with the fewest genetic
flaws for gestation. Single cells can be removed from an embryo up to the
blastula stage (in which there are from eight to a couple hundred cells) and
the DNA assayed for about 75 genetic conditions today, but shortly after the
Human Genome Project is completed there will be hundreds, perhaps thousands of
characteristics that are amenable to analysis. By then the ability to
synthesize different forms of genes and groups of genes, to inject them into an
embryo, and to have them "take" and be expressed properly will no
doubt be perfected. It has already been done with some success in dogs, fruit
flies, and of course, bacteria. (Such manipulations are much simpler in plants,
which explains the early successes in agriculture.) Probably within ten years
from now it will be possible to engineer human designer children as easily as
we now do with crops. Social constraints will of course prevent immediate
application of such techniques in the United States and Europe, but the
technology will be world-wide, on the internet, and scientists willing to
undertake the work will not be hard to find. People will be able to select not
only the gender of their baby, but its height, build, coloring, tendency to
obesity, resistance to several mental diseases including depression and
schizophrenia, immunity to hundreds of physical diseases, many aspects of
intelligence and personal gifts such as musical and artistic talent, athletic
prowess, mathematical and analytical ability, leadership qualities, even
elements of character such as a tendency to be brave, honorable, or monogamous,
and to have an adventurous spirit. We can even endow them with a long, long
life, perhaps 200 years or more.
But even more amazing is the prospect of genetic medicine, and it is almost upon
us already. A biopsy specimen of cancerous tissue will enable the culturing and
DNA analysis of each individual malignancy so that a specific, unique
"magic bullet" can be fashioned, the precisely perfect treatment down
to the last atom. Antibiotic sensitivity will no longer be a problem, for the
same reason. The hundreds of genetic diseases that we are heir to will likewise
be treatable, and it will be possible to grow new limbs and organs that will
never be rejected by the body.
This will all be easier than most of us now think, because a lot of growth is
automatic, in the same way that many molecules and nanostructures have been
shown to auto-assemble themselves, given the precursors. I was amazed to learn
just a couple of weeks ago that this is already being done with urinary
bladders-only in research dogs, so far, but humans are next. A one-centimeter
square piece of bladder can be grown into a fully functional organ in only
about six weeks, and when implanted back into the dog, blood vessels and even
the nerves grow back, so that conscious control is restored! That was utterly
unexpected. Imagine: no more inconvenient, smelly bags! Remember, this is just
tissue culture, without any genetic engineering. Let me give some examples of
genetic medicine that are being successfully practiced in lab animals and in
humans right now, today.
In January, two research groups reported success in reversing hemophilia B in
dogs, using the gene that codes for the clotting protein known as factor IX.
They put it into disabled adenoviruses and injected them into the animals.
Injection into leg muscle was not very efficient, increasing the concentration
of factor IX by only 1.4 %, but it was sufficient to prevent most of the dogs'
spon-taneous internal bleeding. Injection into the portal vein, which supplies
the liver where production of factor IX occurs naturally, was much more
effective. Both approaches seem to be permanent-all animals continue to do well
after 18 months.
In an ironic twist on the notorious role of tobacco in producing tumors,
scientists at a company in California have succeeded in inducing tobacco plants
to mass-produce effective antigens against non-Hodgkin's lymphoma. It turns out
that the tobacco mosaic virus is an excellent vector for getting foreign genes
into the plants. Literally every cell becomes infected, the yield is
phenomenal, and it takes only two or three weeks to produce a "crop"
of the new protein. The researchers used biopsy material from a mouse B
lymphocyte lymphoma to produce a fragment of the DNA that codes for its
characteristic surface antibody, put it inside specially prepared viruses, and
injected them into a tobacco plant. Within a week the plant was producing the
antigen in every cell, and within a month it had produced enough new protein to
test. When injected into the mouse with that lymphoma, the antigens from the
tobacco plants induced the mouse's system to make antibodies that effectively
targeted the lymphoma cells. Even more significantly, this vaccine protected
other, healthy mice injected with the lymphoma cells. It worked like a charm on
the first try.
People who require more than one cardiac bypass or balloon angioplasty are
dreaded by thoracic surgeons, because they seldom fare well. Doctors in Boston
have injected DNA coding for a piece of the gene called vascular endo-thelial
growth factor, which directs blood vessel growth, into the damaged,
blood-starved heart muscle of human patients who have had several bypass
operations but are still doing poorly. After three months, six of the eleven
patients were entirely free of angina, and the overall use of nitroglycerin
tablets by all eleven combined fell from an average of 60 pills a week to just
2.5-another impressive success on the first try. And this involved nothing more
than injecting the naked DNA directly into the heart muscle-no virus vector
required.
Finally, there is hope for people afflicted with the frailty of old age-which
is all of us, eventually. Researchers at the University of Pennsylvania placed
DNA coding for "insulinlike growth factor 1," a growth hormone, into
disabled viruses and then injected them directly into the muscle of one hind
leg of young, middle-aged, and elderly mice. After a few months of sedentary
life, the treated leg in the young mice had 15% more mass and strength than the
control leg. The effect was even greater in the geriatric mice: they showed 19%
more mass and 27% more power in the treated leg, thus preserving their physical
condition at young adult levels. Another near bulls-eye on the first try! Not
only does this give promise of a real fountain of youth, it should also be
effective in other muscle tissue, such as the heart. The effect has been
expressed only locally so far, so people would require many injections to cover
all their muscles. Cardiac therapy would need fewer injections, but in any
case, it would only have to be done once. This is fantastic! I'm ready to sign
up for this treatment right now.
These are only the first tentative forays into the new realm of genetic
medicine, but wholesale application is, in many cases, just an FDA ruling away.
And that brings me to the second usage of my new word, nanoculture: the
ability to culture these brave, new nano-products in molecular biology
laboratories so quickly and easily will, I believe, create a new world
culture-a sub-culture unique to our time, as illegal and lucrative as the drug
subculture, as pervasive and furtive as the homosexual subculture, all because
the U.S. Food and Drug Administration will try to control genetic medicine, and
they will fail.
The FDA is still smarting from the Dietary Supplement Health and Education Act
of 1994, which was enacted by Congress in response to a major grass-roots
movement. The agency had attempted to control the marketing and sale of
mega-vitamins and other "natural" drugs for years, until finally, the
producers got organized. They prepared standardized protest letters and
included them with the packages, which millions of people signed and mailed to
their representatives in Washington. Congress responded by making this new law
that classified all naturally-derived products as "food," thereby
preventing any interference from the FDA for the sale of anything that is
simply extracted and concentrated from any living organism, including human
hormones and metabolites. "Anything that God makes cannot be
prohibited," went the mantra. That's why it is now possible to buy things
like DHEA and melatonin, which I take daily, without a prescription. The most
the FDA can do is prevent them from making direct health claims. I guess
promises that these dietary supplements "promote healthy skin" or
"increase energy" or "help improve memory" don't count as
real medical claims. Of course, the gullible public knows exactly what the
producers want them to think such language really means, and the FDA is
extremely unhappy about it.
I believe the new and upcoming genetic medicines will eventually be removed
from the FDA's purview also, but by a different process and with a different
denouement. Unlike simple natural extracts like vitamins and hormones, these
new medicines will be too expensive for most people to buy, and a grass-roots
approach will not work. Instead, a small cadre of wealthy people will be the
vanguard, and they will get their way simply by threatening to withhold
millions of dollars from politicians' election coffers. But before that, there
will be a chaotic period of several years during which the FDA will attempt to
criminalize the purchase and use of these unregistered and unapproved drugs. I
believe one of the reasons they will fail is that they will be unable to find
them and interdict them. Another is the personal power of wealth and
influential people. Speaking of lymphoma, who would try to arrest Jacqueline
Kennedy Onassis or King Hussein, who both died of that cancer?
Perhaps some of the early gene products will require refrigeration during
transport and careful dispensing by physicians, but eventually many of them
will be as stable as any other virus, and just as easy to "catch" as
a cold. Even if they must be injected, syringes are not hard to get. But
imagine a genetic drug that can be micro-encapsulated and simply sent through
the mail like a letter and then taken into the body with a scratch-and-sniff or
scrape-and-swallow exercise. FDA would never be able to control that kind of
commerce. Purveyors will be on the internet; the word will get around (on the
internet) that, for example, Dr. Wong in Singapore has a superior product; a
surreptitious deal will be struck; Dr. Wong may ship the material to any of a
thousand intermediate handlers anywhere in the world, who will relay the
merchandise to its final destination. If you think this sounds a bit like
"dealing drugs" such as cocaine and heroin, you have gotten my point.
A new illegal drug culture will develop, exactly analogous to the lawlessness
of the Prohibition era in the '30s and the Drug War in the present. There won't
be goons with machine guns in the streets, but it will create a pervasive
contempt for the law among the middle and upper classes that will be every bit
as corrosive to the republic. I believe one of the fallouts of this dark,
lawless nanoculture will be the crippling, if not the destruction, of the
FDA-at least, its drug approval and enforcement activities.
I believe another fallout of the coming nanoculture is that the huge,
multi-national chemical/drug companies-the ones that are now abandoning their
core businesses and jumping on the bandwagon created by the promise of the
Human Genome Project-will lose their investment. They will try to patent
everything they can, but the Dr. Wongs of the world will ignore them. It
doesn't take much of a capital investment to manufacture a batch of DNA made to
order-much less than a million dollars today-and the cost of the sequencing and
synthesis machines will go down like the prices of cameras and calculators. All
of the intellectual property needed will be readily available over the
internet, and there will be nothing to stop the thousands of small entrepreneurs
scattered all over the globe.
It will be a strange time, with the most amazing and fabulous products being
shipped via the most mundane and innocuous routes, like the Hope diamond was
mailed to The Smithsonian Institution. It makes me think of the closing lines
of Sidney Lanier's great poem:
"And
now from the vast of the Lord will the waters of sleep
Roll in on the souls of men,
But who will reveal to our waking ken
The forms that swim and the shapes that creep
Under the waters of sleep?
And I would I could know what swimmeth below when the tide comes in
On the length and the breadth of the marvellous marshes of Glynn."
1999
by William H. Beauman
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