Analog SFF, June 2011 (13 page)

The next visit, if there was one, he would take the chopper!

From the bottom deck they climbed endless flights of stairs, not stopping until the helipad level. Barrels and bulky gear lay scattered across the helipad. To deter unauthorized landings? “You really don't want visitors, do you?"

Kayla just shrugged.

He grabbed his cap as a wind gust snatched it from his head. Vibrations his earplugs would not let him hear crept up his legs, shaking his entire body.

The California coast sprawled in the distance. Kayla, who had saved her breath for the long climb, resumed her spiel. “Lots of oil platforms are like this. Near enough to land for easy resupply. In water deep enough to offer a significant temperature differential. Generating power by dropping pipe here is less disruptive than laying pipe from shore out to deep water."

Compared to some projects Dillon had assessed, this was environmentally sound. Sun would heat the surface waters no matter what. It would be better that obscenities like this platform had never been built, but at least with OTEC the platforms might contribute clean power.

Except that nothing built on a scale this monstrous could ever be benign...

"This pilot project will generate, if I remember correctly, five megawatts?” Dillon asked. “How do you deliver the power to where it will be used?"

"Converted to microwaves.” She gestured across the helipad to a sturdy metal tower studded with antennae directed to points around the compass. “The small dishes will beam power to nearby drilling platforms, which will no longer need diesel generators to have electricity. The big dish"—which was not all that big—"will beam to the receiving antenna under construction on Santa Cruz Island. I guess visitors at the Nature Conservancy's research center aren't ready to give up supercomputers and hairdryers.

"The microwave tech isn't much different from how the NASA powersat will transmit power to the ground, except that we aren't pushing the state of the art. We're dealing with megawatts, not gigawatts, and sent over a much shorter distance."

Powersats: The most mega megaproject of them all. If Kayla understood what mattered to Dillon—and, of course, she could not possibly—she would have picked a different example. Likening her endeavor to powersats had turned his stomach.

In her ignorance, she kept talking. “Of course not every OTEC facility will use beamed power. Where we lack a line of sight to land, and maybe for really large-scale generators, we expect to run marine power cables. You know, like the big offshore wind farms use."

And Dillon suddenly knew exactly what monkey wrench to throw into these particular works. “I have interests in a superconducting-cable start-up.” Even though the bunch in Illinois did not yet know it. They had been eager enough to get some of his money.

"Zero-resistance underwater cables to the power grid on shore. Of course, that would be great.” Kayla hesitated. “At the capacities we'll need, superconducting cable is experimental at best. We've got a lot on our plates as it is."

"No, this could work,” Dillon said firmly. “Look, I'll put my cards on the table. One-of-a-kind investments aren't worth my time. I look for synergies, win-win situations. Here we have one. The other bunch would get an impressive, real-world demonstration. You would get first crack at a more efficient way to bring OTEC power ashore."

"Does this mean my company has your backing? That you
will
invest?"

Dillon gazed out across the Santa Barbara Channel, saying nothing, the breeze whipping his hair. She could do the math.

She straightened, squaring her shoulders. “If you back Jorgenson Power Systems at the funding levels we've discussed, we'll assess our fit with your other company."

"That's all I'm asking."

Because commercializing technology of this scale would involve several more rounds of capitalization. Getting follow-on investments was all but impossible without the tangible endorsement—second-round buy-in—of the earlier investors. So: Kayla's people
would
factor the new technology into their plans. Just as, when Dillon called to dangle a bit of venture capital, the Chicago bunch would swallow hard and agree to a marine deployment—
despite
the complexities that would introduce—for their first big field trial.

With a few million bucks of other people's money, he would tie
both
ventures in knots.

To be continued.

Copyright © 2011 Edward M. Lerner

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Our July/August double issue takes full advantage of its extra spaciousness to bring you an extra-wide variety of fiction, fact, and special features. Kristine Kathryn Rusch leads off with another novella in her “Retrieval Artist” series, though this one is “off to the side” of what you've seen before, focusing not on a Retrieval Artist but on something new and different. Richard A. Lovett appears twice, with a novelette, “Jak and the Beanstalk,” bringing a decidedly novel twist to an idea familiar to SF readers if not the general public; and another article in his popular series about fiction writing, this one dealing with narrative voice. James Gunn, an important force in getting science fiction some respect outside its “ghetto,” has another special feature examining a science-fictional view of our digital future.

We'll have not one, but two science fact articles: one by C. W. Johnson on the fascinating physics up to string theory (and what may lay beyond), and one by astronomer Kevin Walsh on the unlikely-sounding subject of why Proxima Centauri may not be the nearest star after all.

Plus all our usual columns, still more stories by writers including Kyle Kirkland, Scott William Carter, and Ernest Hogan—and, last but far from least, Part 2 of Edward M. Lerner's serial
Energized
.

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The use of nanoparticles as vehicles for delivery of medications to appropriate sites in the body is an area of active current research. These particles have some interesting properties, although they are a far cry from the “nanobots” of science fiction. We do not have nanoscale factories in which we can simply build nanomachines. Instead, we must rely on the natural proclivities displayed by atoms and molecules when mixed together and subjected to achievable conditions of temperature, pressure, pH, et cetera, in macroscale laboratory settings. One consequence of the fact that we cannot make nanobots is that “targeting” of nanoparticles in the body is a matter of selective binding or retention of particles that circulate passively in the blood. The chemical nature of nanoparticles also imposes limitations on their capabilities and creates some rather unique toxicities that could limit their usefulness in medicine.

Nanoparticle drug delivery systems are, nevertheless, being studied for treatment of a variety of diseases and conditions—everything from tuberculosis to irritable bowel disease. They have been considered for pain management and are promising candidates for therapeutic penetration of the blood-brain barrier that blocks many drugs from acting on the central nervous system. A large proportion of the work on these systems has, however, been in the area of cancer treatment. This research bias is perhaps not surprising, since cancer is a major killer that is yielding only grudgingly to medical science. In addition, anti-cancer drugs are notorious for being only moderately more toxic to cancer cells than they are to normal cells and tend to have rather nasty side effects. Nanoparticles seem tailor-made to improve this situation and drugs delivered this way show improvements in therapeutic index (the maximum non-toxic dose divided by the minimum effective dose).

Advantages of nanoparticles

A nanoparticle drug delivery system usually consists of at least two components: the drug or therapeutic agent, and the particle, which is a vessel or vehicle for the drug. Such systems can, of course, have more than the minimum two components, since additional molecules can be attached that modify the behavior of the system or add additional desirable properties, such as improved biocompatibility, increased half-life in the circulation, or targeting to a specific site in the body. A natural advantage of two-component nanoparticle drug delivery systems is that the drug itself does not have to possess all of the characteristics that would be optimal for its use as a therapeutic agent. The drug might be insoluble or very toxic to cells in general (as is the case for many anti-cancer drugs), and the particle could provide a water-soluble carrier to mask the drug's toxicity until it reached its target. Or the drug might have poor chemical properties for passing across cell membranes and the particle could circumvent this by having surface characteristics that cause it to be readily taken up by cells. Another possibility is that a drug may be too rapidly broken down by the body to be effective. In this case, the use of an enclosing nanoparticle can protect it from degradation long enough for it to have a therapeutic effect. In a situation where the drug needs to be taken up by a target cell, the particle can persist inside the cell, resisting breakdown by the cell's protective enzymes and releasing the drug slowly over an extended period of time, resulting in superior timed- release behavior.

A major attraction of nanoparticle delivery systems is the enhanced ability to target a drug to a specific cell type. Antibodies directed against cell-surface molecules that are specific to a given cell type can be attached to the surface of the particle. In addition, some types of cells have receptor molecules on their surfaces that will bind to a specific ligand molecule and cause it to be taken into the cell's interior. While it may be possible to physically link a targeting antibody or ligand directly to a drug molecule, the physical linkage can interfere with the desired action of the drug. Attaching the targeting molecules to the nanoparticle instead of to the drug itself has the obvious advantage of preserving the drug in an unmodified condition.

Size and physical characteristics

For the purpose of drug delivery via the blood, particles should preferably be no more than 100 nm in diameter, because larger particles are more rapidly removed from the circulation by stationary macrophages in organs such as the liver, spleen, and lymph nodes. These macrophages are phagocytic cells whose purpose is to engulf and digest particles floating around in the bloodstream that might be harmful, such as viruses or clot-initiating debris. Surface characteristics are important in enabling nanoparticles to avoid capture by these cells. In general, the surface should be hydrophilic rather than hydrophobic, and biologically derived polymers are often used. Hydrophobic and non-biological materials are more likely to attract the attention of the phagocytes due to a process in which various molecules, termed opsonins, bind to the particle's surface and act as flags marking the particle for destruction. The synthetic polymer polyethylene glycol (PEG) is apparently not “seen” by opsonins or by phagocytic cells, and nanoparticles are often coated with PEG (PEG-ylated) to “stealth” them so that they will not be cleared so rapidly from the circulation.

To put the size of nanoparticles into perspective, a water molecule is about 0.16 nm in its largest dimension, buckminsterfullerene (C60) is about 0.73 nm in diameter, a naked DNA strand is a little less than 2 nm in thickness, and a molecule of hemoglobin is about 6.4 nm across (dimensions from Faraji and Wipf). The lower end of the nanoparticle scale thus overlaps the size range of biologically important macromolecules. The size of nanoparticles is potentially adjustable, which is part of their appeal. Particles must be large enough to accommodate useful amounts of drug, but smaller particles have higher surface-to-volume ratios than larger particles. If a therapeutic agent is stored in the interior of the particle and released at the surface, varying the particle size allows some control over the rate of drug release from the particle and the length of time the drug will be available in the body.

Types of nanoparticles

A number of types of nanoparticles have been investigated or considered for use in drug delivery. These include solid, hollow, or porous inorganic particles; carbon-based particles such as fullerenes or carbon nanotubes; various types of lipid-based particles; virus-based nanoparticles; and polymeric nanoparticles or micelles. In a 2008 review article, Cho et al. provide examples of all except the first type (inorganic particles) for use in treatment of cancer, although most were at that time either in clinical trials or still in development. Liposomes, a kind of lipid-based nanoparticle, containing the anti-cancer drugs doxorubicin and daunorubicin have been approved by the FDA for treatment of metastatic breast cancer and AIDS-related Kaposi's sarcoma.

Inorganic nanoparticles can be composed of silica, metals, or metal oxides or sulfides. Such particles could be solid, with the drug attached to the outer surface. Gold nanoparticles have been prepared for use in this way. Inorganic drug carriers could also be a hollow shell with pores opening to the inside or a solid particle with interconnecting pores passing through it. Such inorganic nanoparticles are very stable with respect to temperature and pH, but they are not biodegradable and dissolve only very slowly and so may present problems of toxicity, especially if used for long-term treatment. Gold particles are non-toxic and very biocompatible, but must still be cleared from the body since they do not biodegrade. For these reasons, inorganic nanoparticles do not seem as promising for drug delivery as the other types of particle discussed below in greater detail.