"Nano, Right Under Our Noses"
by Jonathon M. Sullivan
(date of first publication November 1997)
Those poor nano guys.Since 1974, Nano Guru Eric Drexler and his growing cult of nanotech acolytes have been breathlessly articulating a shimmering vision of the future in which man moves atoms about like tinkertoys, enjoying an almost godlike command over matter. In the NanoFuture, our bodies will indestructible and immortal, our tissues fortified with nanopolymer and our bones reinforced with diamond rebar. In the NanoFuture, we'll build computers the size of viruses, grow starsails out of one pound payloads, and spin intelligent textiles out of automated vats. With our fantastic control of matter, we'll eradicate hunger and not just prevent but actually repair environmental devastation. In the NanoFuture, we'll conjure products out of thin air, assembling them out of an invisible "utility fog" of micromachines and raw components.
Except the NanoFuture is, for the most part, nowhere in sight. No microscopic robots. No molecular assemblers or replicators, no rod-logic microprocessors built out of a few thousand atoms of carbon. Elaborate designs for molecular ratchets, robot arms and gear trains abound, but nothing really substantial has been built on the nano level. As far as I'm aware, not a single sector of industry has used any sort of nanotechnological process to build stuff and make money.
Perhaps the worst sign of all for nanotechnology is that even the world of science fiction has begun to look askance at the nano "revolution." Emerging from the worn-out cyperpunk future, searching for invogarating new ideas and landscapes, science fiction took to the NanoFuture like Bob Dole to Viagra. But nanotech is being recognized as an all-too convenient device for authors to wave their hands and spout all kinds of unlikely technologies, magical thinking, wish fulfillment and out-and-out bullshit. It's begun to wear thin.
Don't get me wrong. The Diamond Age blew me away, too, and one has only to read my last column to see that I've got high hopes for nanotechnology. Nanotech remains an important and vigorous idea in sf. And sf remains an important ally for the embryonic discipline--if people can dream it up, and if it doesn't defy the laws of physics, eventually they'll do it. Nanotech in the real world is making some progress, in areas such as scanning tunneling electron microscopy, self-assembling monolayers, nanotube fabrication, buckyball chemistry, and so on. And science fiction's exploration and illumination of the potential of nanotech gives it a sort of inevitability, even if it doesn't eventually take the forms we anticipate.
Which is what I want to talk about. Suppose I told you that molecular machines are being used in laboratories all over the world, that we can string small molecules together into all kinds of structural, catalytic and mechanical nano-products? Suppose I told you that I myself have used an "assembler," a catalytic molecular scaffold, to build microscopic motors, circuits and chemical processors?
Well, I have. And so have you. You do it in every cell of your body, all the time.
The greatest argument that Drexler and his acolytes can offer up to the Nattering Nabobs of Nanotech Negativisim is that it's already been done. In a sense, it's the oldest "technology" on earth. Molecular machines are the basis of living matter.
Some of you are shaking your head and saying: it's not the same thing. What we all do in our cells is one thing, but the dream of nanotech is to build stuff in the laboratory and factory. And don't give us a biotech spiel: growing up insulin in vats of E. Coli is not the same thing as nanotech!
No, it's not. But biotechnology and nanotechnology must converge, must dovetail into sister disciplines. It is inevitable, for two reasons. First of all, they both seek to manipulate matter at the atomic and molecular levels. And second, because living systems offer us the machines needed to get nanotech off the ground, the very machines the nanotech gurus have themselves failed to produce.
Let's start with the Assembler. The Assembler is one of those keystones of nanotechnology, a microscopic robot that accepts instructions from the designer or fabricator, and then uses molecules as raw materials to construct a machine or substance. The Assembler has the attributes of an information processor, construction scaffold and chemical catalyst or reactor. So far, a real, honest-to-goodness Assembler hasn't been built de novo. But there's a microscopic machine that's been known to us for decades that does all these things--cheap, available, well-understood and fantastically efficient.
It's called a ribosome.
Ribosomes are multi-component machines built out of RNA and protein. They are found by the millions in all cellular organisms, and are remarkably uniform in structure all the way from bacteria to humans. These remarkable molecular robots are factories for making proteins. Every protein molecule in your body was built on a ribosome.
A ribosome is assembled from multiple parts. It consists of a small subunit and a large subunit, stacked one atop the other like a truncated snowman. The ribosome assembles only when an instruction for protein synthesis comes along--pretty efficient. The instruction is in the form of messenger RNA, made in the nucleus when the cell reads the genetic blueprint from DNA. The messenger RNA is just a string of ribonucleotide monomers, essentially one long sentence made up of many "words." When messenger RNA appears in the cytoplasm, small and large ribosome subunits glom onto it and move along the string, reading the directions. Simultaneously, the ribosome recruits amino acids to build the protein. All proteins are strings of amino acids. There are about twenty amino acids in biological proteins, and they can be combined in millions of ways to yield proteins with a fantastic variety of structures and functions. The type of protein you get depends on how you string together those amino acids--which in turn is determined by the genetic "instructions" carried in the messenger RNA.
Once the ribosome has recruited two amino acids, it holds them close together on its surface and catalyzes the formation of a peptide bond, the chemical link that holds amino acids together. Then it reads the next "word" in the messenger RNA's instructions, brings in the next appropriate amino acid to the platform, and forms another peptide bond, adding to the growing protein chain. When manufacture is complete, the protein folds up into the shape needed to do its work, the ribosome disassembles, and the messenger RNA is degraded. All the components recycle, to be used again and again.
Figure 1. The Ribosome. A ribosome is composed of a large subunit and a small subunit, which assemble around the messenger RNA. The ribosome moves along the mRNA, "reading" the message that codes for the sequence of amino acids. Transfer RNA (tRNA or T) fits into slots on the ribosome to introduce new amino acids into the growing protein chain.
So--ribosomes are information processors. They read messenger RNA and use the data to do their work. They are mechanical platforms, physically manipulating molecules to bring them into useful juxtapositions. And they are chemical processors, catalyzing the formation of peptide bonds. What's more, ribosomes, with the help of associated protein factors, assemble themselves. Sounds like nanotechnology to me.But wait, you say. It's all very well that ribosomes can build stuff inside cells. But that's not the same as a bona fide ex vivo industrial process. And you can only use a protein to do what it was designed to do. Make enzymes, beefsteak, and hair. It's still just biotech, not real nanotech.
Except that ribosomes work very well outside of cells. It's called "in vitro translation," and it's been a standard tool of cell biologists for quite some time. Ribosomes can be harvested from cells, suspended in buffers, provided with energy (in the form of adenosine triphosphate, ATP, the energy currency of virtually all living systems), messenger RNA and amino acids, and they'll just go to town, cooking up any protein for which you know the RNA sequence.
And what about those proteins? They, themselves, are molecular machines and miracle materials. Protein is what makes up keratin, the stuff of fingernails, rhinoceros horn and Dennis Rodman's hair. Protein is what makes up collagen and elastin, the remarkably rugged underpinnings of skin and joints.
Proteins are the building blocks of "cell signaling systems"-- vast, branching, interlocking arrays of relay molecules that allow the cell to exquisitely regulate its physiology. These cellular cybernetic systems are only beginning to be understood, but already have invited comparison to integrated circuitry. This analogy has proven even more compelling in recent years as we have begun to understand that cell signaling proteins don't simply float around the cell and slam into each other randomly to convey their message, but rather that they are arranged on membranes and in semi-crystalline arrays within the cells, spatially organized in such a way as to promote the transmission of message.
Proteins make up enzymes, the amazing molecular machines that catalyze all chemical reactions in living systems, generally by bringing two or more chemical components into a proximal spatial arrangement and catalyzing the formation or degradation of a chemical bond. In this sense, enzymes are like ribosomes, but protein enzymes come in a fantastic variety, performing such diverse tasks as splitting the glucose from your morning grapefruit to recycling the neurotransmitters swimming in your brain as you read this article.
Proteins form the motors for the ciliated cells in your lungs and central nervous system. Proteins form the exquisite cytoskeleton infrastructure of our cells, composed in part of the highways of microtubules that ferry the traffic of the cell, like parts moving along an assembly line. Proteins form the gears, pulleys and ropes of actin, myosin and troponin that give our muscles the mechanical ability to contract. Proteins form ion pumps that build the electrical potential gradient of about 60 millivolts that exists across the membranes of every cell in your body, billions of little batteries. And proteins also form the ion channels that allow these membrane batteries to discharge, millions of little capacitors, switches and circuit breakers that make it possible for our hearts to beat, our muscles to pump, our brains to think.
Just about any machine you can think of.
That's fine, you say, if you want to pump ions out of a cell or grow Dennis Rodman's hair. But is that nanotech? We're stuck with the enzymes and proteins nature gave us.
Perhaps. But these proteins can be used outside of the cell, just as ribosomes can. Ion channels can be trapped in vesicles of oil, and their current detected. Microtubules exactly like the ones in our cells can be grown on glass and then made to crawl across the surface with a little ATP. Actin and myosin seek each other out in a buffered saline solution. Protein antibodies can be custom-designed to pick out a single chemical from a complex stew, then mounted on glass beads in separating columns. And enzymes can be used to conduct complex chemical reactions in vitro--and at room temperature and pressure, without toxic intermediates.
Still, it would be irksome to be limited to natural proteins. But we aren't! Ribosomes will make any protein you tell 'em to, natural or otherwise. And there's an infinite number of possible amino acids besides the twenty used in nature. Any stable chemical side chain you want can be stuck onto an amino acid backbone, yielding a virtually limitless array of amino acids and proteins, with a virtually limitless range of chemical and mechanical properties.
The problem then becomes how to design the protein machines you want. But again, nature gets us on our way. We are finally making some progress in predicting the three dimensional shape and chemical-mechanical function of a protein based on its amino acid sequence. Further research will give us the tools we need to engineer any kind of protein we want and determine its sequence. Then, using technology that exists today, we translate the sequence into genetic code, cook up the necessary RNA, and feed it to our ribosomes. Voila! You've just used a nano-assembler to make a nano-machine. You're doing nanotechnology.
This isn't the entire solution to nanotech's problems. Custom designing an enzyme that'll grow diamond by the vat is still a ways off, I'd venture. And it'll be inconvenient, to say the least, to restrict all industrial nano-processes to solution, or the temperatures and pressures used by living systems. But it's not hard to imagine that if we can figure out how proteins fold at room temperature and physiologic pH, we can figure it out for other systems. Eventually, somebody will come up with "solid state ribosomes" that function on fixed substrates. Somebody else will come up with alternatives to the peptide bond -- a variable monomer other than the amino acid, with a synthetic "ribosome" and "messenger RNA" to go along with it. Then our "proteins" will be plastics, or organometallics, or even completely inorganic.
These innovations will free us from using biological molecules. Then it'll be blue skies, but nanotech will only fly because it got a foothold in the world of ribosomes and proteins. And even when humans start building machines out of materials that no living system would tolerate, to perform functions we can now only imagine, we'll still be using the basic components and strategies borrowed from our own cells, the nanotechnology that's been right under our noses for a long, long time.
Here's some URL's for those interested in ribosomes and nanotechnology:
http://server.cs.stedwards.edu/contrib/Chemistry/CHEM43/Ribosomes/Ribosome.HTML
http://nano.xerox.com/nano/
http://www.imm.org/PNAS.html
http://www.rand.org/publications/MR/MR615/mr615.html
http://nano.xerox.com/nanotech/nano4/merklePaper.html
