[Footnote 4: The research discussed above uses only one type of quantum dot at a time. But the same quantum effects that give quantum dots their name turn out to mean that their size determines the color with which they glow. Thus, it's possible to tag a cell with many different dots, each fluorescing a different color, each with different antibodies. “One of our colleagues was able to squeeze in seventeen colors,” Tulsky says. This opens the door for researchers to tag many different types of molecules at once, watching their interactions—an extraordinarily powerful tool for figuring out complex biochemical systems.]
* * * *
Bursting Bubbles
Slightly larger are microbubbles.
As the name indicates, they're just that—bubbles of gas, confined in a microscopic shell, typically five microns or less. That makes them bigger than quantum dots, but smaller than cells: small enough to disperse into capillaries throughout the body.
The shell is typically made of something like albumin. The interior is an inert gas, such as a fluorocarbon, which doesn't easily diffuse through the shell, so the bubbles don't deflate.
One use for microbubbles is in ultrasound imaging.
Ultrasound imaging is like pinging the body with sonar to map what's beneath the skin. What makes microbubbles useful is that they don't reflect ultrasound in the same way as the surrounding tissues, allowing you to map either the tissue, or the distribution of bubbles, at will.
Tissues simply reflect the incoming signal. When the signal is set at very low power, that's also what microbubbles do. But if you turn up the power a bit, they start producing harmonics, as well. Hit them with the right frequency and they'll ring like microscopic bells. At high acoustic power, the bubbles break, in the process making a very large noise (at least by ultrasound standards).
So, what can we do with this? A lot, says Jonathan Lidner, a cardiologist at Oregon Heath & Science University, because the nonlinear manner in which the bubbles respond to signal power means it's possible to map both tissues and bubbles, simultaneously.
For example, would you like to find out what parts of the heart are still receiving good blood flow after a heart attack? Inject the patient with microbubbles and see if any at all are reaching the damaged tissue. Then, blast the area with a loud ultrasound pulse and see how long it takes for new bubbles to reappear. You can do the same in the brain, to look for stroke damage. Or you can look for vascular changes associated with tumors and tumor growth. Even without zapping the bubbles, the imaging gives you a nice roadmap of the tumor's blood vessels. The gas from the burst bubbles, by the way, poses no risk of blocking other blood vessels; there's just not that much of it.
Even more is possible. In 2003, a team led by Dilantha Ellegala of the University of Virginia School of Medicine published a paper in Circulation, the journal of the American Heart Association, which showed that, just as quantum dots can be conjugated with antibodies, so too can microbubbles.
This can be used to cause them to bind to tumor biomarkers, allowing ultrasound to find tumors that might not show up. Or they can be coated with antibodies designed to seek out inflamed tissues, such as inflammatory bowel disease or very early atherosclerosis. And “very early” means very early. “As a cardiologist, I want to [be able to] detect which of you is going to develop cardiovascular disease decades before it happens,” Lidner said at the nanotechnology meeting.
The bubbles also have tremendous prospects for disease treatment, ranging from cancer cures to a possible way to zap even the most antibiotic-resistant bacteria.
The idea is that instead of putting a gas in the antibody-tagged bubbles, you pack them with a drug.
This has several advantages over conventional pills and injections. To begin with, the drug doesn't have to contend with bodily processes that might degrade it in the stomach, intestines, or bloodstream. But the real advantage is the ability to pop the bubbles on demand. Microbubble treatment would begin with an injection, followed by a wait, while the bubbles find their targets and bind to them. Then, you zap the desired tissues (the whole body, if necessary) with a strong ultrasound pulse, bursting the bubbles, and delivering high concentrations of the drug exactly where it's needed. That not only jacks up the drug's concentration at the target site, but minimizes side effects: a major boon for cancer chemotherapy, and potentially a way to make really potent antibiotics.
Even better is an effect discovered in 1917 by Lord Rayleigh (who in 1904 won the Nobel prize in physics for his discovery of argon gas).
At the time, the British navy had a problem: propellers on fast-moving ships were wearing out at an unexpectedly rapid rate. Lord Rayleigh's task was to find out why.
The problem turned out to be cavitation, which occurs when the propeller's rotation creates a low-pressure zone in which air bubbles form, then burst. This turns out to be a very powerful process that pocks even the metal surface of propellers.
Well, microbubbles are bubbles. And their antibodies can link them to cell walls, maybe of tumor tissues, maybe of nasty bacteria. Then we can pop them. “We don't do anything as bad as destroying metal,” Lidner says. “But we do use the energy of destroying bubbles to enhance delivery.” More precisely, the cavitation effect of the popping bubble can be used to squirt its contents through a cell wall. Alternatively, if the microbubble is merely passing through a capillary within a tumor, popping it with a carefully directed ultrasound pulse can squirt its contents out of the capillary and into the tumor.
It's not really a microscopic submarine, on a cellular-level seek-and-destroy mission. But the end result isn't all that different.
And so it is likely to be with most biological nanotechnology, at least for the foreseeable future. Rather than “bots,” as conventionally envisioned by science fiction, our medical nano-tools will be single function, and simpler in design. But the things they can do will be as complex as biochemists’ imaginations can make them, taking advantage of cellular-level processes we're only now beginning to understand.
* * * *
About the author:
Richard A. Lovett has written more than sixty articles and stories for Analog since his first appearance in 1999. A full-time writer for more than two decades, he keeps fresh by regularly changing fields. The most recent switch was to sports reporting for the U.S. Olympic Team trials. A former law professor, he has degrees in astrophysics, law, and economics. He also worked for a couple of years for an environmental engineering firm, where he absorbed some chemistry by osmosis. He then spent more than a decade writing hundreds of articles about toxicology and biochemistry, fueling his interest in medical nanotechnology.
Copyright (c) 2008 Richard A. Lovett
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Probability Zero: ALIENS by Rick Norwood
Conrad Montcastle ate a seedless grape and a thin wedge of Camembert cheese. He took a sip of fine Aldebaran wine. The main course had been cleared away, and only the men remained at the table. His gray eyes narrowed. He was a strong man, in the prime of life, and he was not the sort of person to back away from unpleasant truths.
"What Doctor Hudson has proposed is the only solution to the current crisis. Unless something is done, the aliens will overrun the earth. But all six of us must agree. The doctor takes the greatest risk, and we cannot ask him to take this risk unless he is assured of our unconditional support. Not only our fortunes and our honor, but our very lives will be at risk if we go ahead with this. We stand or fall as one."
Across the table from him, John Lowell did not flinch from the challenge. “I'm with you. I think I speak for all of us when I say that unless someone steps forward to save this planet, the human race will no longer be able to call Mother Earth our own. These aliens have no morals, no finer sensibilities, and they breed like flies.” His voice rose both in volume and in pitch. “Those fools at the United Nations, they keep on giving the aliens greater and greater ‘rights.’ Rights! What do aliens know of rights? This isn't their planet. Rights must b
e earned. It is insane to talk about rights that they have not earned and do not deserve. If the government will not act, then patriots must step forward. I've even heard talk of giving aliens the vote. Think, gentlemen! They outnumber us. It would mean the end of the human race."
Montcastle noted that John's hands were trembling, but the man's jaw was set, and so he put down the trembling to strong emotion rather than weakness. He looked around the table at the faces of the other men. Their expressions were serious. They were his dearest and closest friends, and he felt sure he could count on every one of them to keep his mouth shut.
From the parlor came the soft voices of the women. The servants had vanished into the back of the mansion and would not return unless Montcastle rang the silver bell near his right hand. “Well, Doctor?"
Doctor Hudson stood and bowed slightly to the group. He was a large man, who wore old-fashioned eyeglasses. “If we are all agreed, I shall begin with my own field hands. I've already told them that under the new laws they are free to travel, to try to find better jobs if they can find them. A few will be loyal and stay, but the majority of them don't know the meaning of the word loyalty. They will disperse across the globe."
He took a deep breath and continued. “Here is the plan. I have told them that they need an inoculation, to protect them from diseases that are found in the big cities. They've never been to the cities, so they don't know any better. They'll line up to be inoculated. I have genetically designed a disease that is highly contagious among aliens, but which cannot spread to humans. It has a gestation period of about thirty days, after which the infected alien will experience a slight fever, then coma, then death. It is the most humane way to deal with the alien problem."
Montcastle nodded. “Very well then, gentlemen. Are we all agreed?” Each man met his eyes, and he saw that they understood. They were in this together, come what may.
He rang the silver bell, and a short, blue servant in a butler's uniform slid softly into the room. “We're ready for coffee and brandy now, L'chok."
"Very good, sir."
He would miss L'chok. The alien had been with his family for generations. But sacrifices were necessary.
* * * *
Six months had passed. It was winter, and the six men were once again assembled. The table setting glittered as before, with fine china, linen napkins, and crystal goblets. But there was no wine and very little bread. From the kitchen came the sounds of the women, cleaning up.
"Gentlemen,” Montcastle said, “This year's crop lies rotting in the fields, the outer planets refuse to extend us any more credit, and good help isn't to be had for love nor money. But at least Earth is once again in the hands of human beings."
"And,” John Lowell added, “nobody suspects us. No one has any idea how the plague started.” He looked significantly at the doctor.
That doctor's jowls shook and the flesh hung loose on his frame, but there was still fire in his gaze. “We did the right thing,” he said. “There is not the slightest doubt in my mind that the current famine is the fault of those goddamn liberals."
Copyright (c) 2008 Rick Norwood
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Short Story: WHERE AWAY YOU FALL by Jason Sanford
Can ideals be too high?
I was dozing in the aerostat's pilot chair, sleeping for the first time since entering near space two days before, when Bee whispered “weapons lock” in my ear. I woke confused—Was I back in my F-35? Had I blacked out from excessive g-forces?—so I yanked hard on the control stick before realizing my old fighter jet was long gone. Instead, I floated in a balloon just below the blockade line. Fortunately, Bee overrode my stick commands. The computer didn't need to remind me that aerostats couldn't do evasive maneuvers sixty kilometers above the Earth, not when the only thing holding us up was an envelope so thin I could literally see through it.
I cursed myself for falling asleep in the pilot chair instead of my bunk as Bee repeated that a targeting laser had locked on us. I glanced out the pressurized cockpit's window. Below, Earth's blue atmosphere curved serenely away. Above, the blackness of space. Only seven other balloons were in sight. None of the aerostats in this part of the mesosphere carried defensive systems, so I guessed someone manning the blockade had discovered our little ruse.
How long does it take a hypervelocity slug to find you? One second? Two? While I waited, I remembered Brother Donald Page. How two decades ago he'd affirmed my destiny with tears in his eyes, telling this short, skinny girl that if she worked hard, she'd reach outer space. Now I was the closest I'd ever get, and my reward was to be shot down.
Well, screw that, I thought, forcing Brother Page from my mind. I started to call up the blockade frequency to curse them out when Bee intoned the best news I'd heard all day: “Dusty, the target lock has switched from weapons to tight beam. Do you wish to receive a NASA transmission from Major Johnie Acaba?"
"Patch him through, Bee,” I said, angry at Acaba for rattling my cage. I forced out a fake smile as his handsome, square-cut face floated before me.
"Hey wannabe, you're nearing no-go territory."
I bristled. Acaba knew how seriously Seekers—even a not-very observant Seeker like myself—took our destinies. “The Beatrice couldn't reach eighty klicks even if I wanted to,” I said, which was the United States’ definition of the edge of space, and where the blockade officially began. “And where the hell do you get off lighting me up with weapons?"
"I was just joking, Dusty,” Johnie said with a grin. “I wanted to welcome you to near space. I know how much it means for you to get there."
I started to smart back to Johnie, but bit off my words. Johnie was so dense he'd never understood my sarcasm. “Gee, Johnie, are we still on joking terms? Wasn't there a bit of awkwardness a while back at the Outpost?"
Johnie frowned. The Outpost Tavern was an astronaut bar in Houston that looked like a combination barn and old-time general store. Johnie and I had been best friends during our time in the Air Force and when I applied to NASA, I convinced him to go along with me. We spent two years training with the space agency, graduated at the top of our class, and were preparing for our first trip to man the blockade when someone—and my money was on Johnie—spilled the beans about me being a Seeker. Never mind that I'd lapsed so far from the faith that my parents’ annual holiday card included a guilt-inducing “Are you still living in sin?” letter extolling my spiritual deficiencies.
But NASA wouldn't listen. Over the last few decades Seekers had carried out a number of high-profile bombings and attacks around the world. There were also rumors that the last cascade event—a chain-reaction debris sprawl caused by too many satellites and too much junk in orbit—hadn't been an accident. That maybe a Seeker sent a satellite tumbling into another in an attempt to obtain the faith's goal of returning humanity to a simpler way of life.
As I'd packed my gear, Johnie said how sorry he was at me getting kicked out. I screamed at him, wanting to know if he'd told NASA my secret. He swore he hadn't, but I didn't believe him. A few months later, I showed up at his launch party in the Outpost Tavern, intending to let bygones be bygones. But my former colleagues protested my presence, causing Johnie to play peacemaker instead of sticking up for me. I stormed out cursing his name.
But I guess Johnie had forgotten all that. “Thanks for everything,” I said. Johnie looked puzzled, then smiled. Like I said, he never understood sarcasm.
"So what are you up to down there?” he asked.
I glanced at Bee's telemetry. Johnie was orbiting a few hundred klicks above me in low Earth orbit aboard the Freedom 2 space station. In a few minutes he'd be below the horizon and out of range. “Tell you what ... you get me into the Outpost, I'll tell everything I know."
"No can do,” he said. “Astronauts only in there."
Astronauts only, my ass, I thought as I disconnected the tight beam, popping Johnie's holographic face like a soap bubble. I'm better than any damn astronaut. Even if I'll
never get to space like I'm supposed to.
* * * *
My parents joined the Seekers before I was born, drawn to the religious movement by the teaching that salvation lay in living simply and reaching one's God-given destiny. Each Seeker's destiny was secret, decreed by your preacher on behalf of God and not revealed to the world until you achieved it.
Even though I grew up in a staunch Seeker community, I never was very devout. While all my friends wore brown chastity dresses or refused to use cells and net access, I obsessed on science fiction novels. I sat through church services reading old Heinlein and Clarke stories. I couldn't recite the hundred and one supreme destinies, but I knew Asimov's three laws of robotics by heart. My parents were embarrassed; the elders appalled. However, Brother Page encouraged my science fiction habit, telling my parents God moved in mysterious ways and had grand things in mind for me.
When I turned eighteen and went to Brother Page for my destiny, to my total shock the preacher said to reach out into space. “I thought we were supposed to live simply?” I asked. “Forsake the distractions of the material world?"
"God's will can be difficult to understand,” Brother Page said with a secretive wink. “But I'm sure you'll manage."
I hugged Brother Page, excited by his encouragement to follow my dream. When my parents questioned my Seeker commitment after I joined the Air Force, I merely told them I was following my destiny, to which Brother Page nodded knowingly. For two decades I screamed F-35s across the Middle East and Asia, studied aerospace engineering, worked toward being the ideal astronaut. And then NASA kicked me out.
To say I was devastated would be an understatement. Even though I hadn't been to church in years, I looked up Brother Page, who now ran a large Seeker congregation outside Houston. We met in his church's main worship hall, which was shaped like a massive planetarium. I entered to find the lights out and a projected replica of the night sky slowly spinning above me.
Analog SFF, December 2008 Page 6
