Analog Science Fiction and Fact - 2014-01

by Penny Publications

  Emilie, standing beside Ursule in the longboat's cabin, spoke into her own wristband. "Henrick, please... you mustn't do this..." She pressed her lips together, her whole face tight.

  "Ah, Emilie," Henrick said. "I'm afraid I must. We'll go no more a-roving, so late into the night.... Or do I mean that other one... Home is the sailor, home from sea, And the hunter home from the hill. It's time, Emilie. No more missions, no more planets for me. It's time for me to stay in one place and do something with what's left of my life."

  "Henrick," Ursule said, "We don't have to lift off for another two hours. Let me just come talk to you."

  "I'm some distance away," Henrick said. "I took a rover and one of the portable consoles. I've been using it to show images to the dust. It turns out I was wrong that it would stop manifesting the conical eye structures. There are dozens of them around me right now. It even lets me touch them."

  "Damnit, Henrick..." Ursule's arm was trembling as she spoke into her wristband.

  There was silence for a few seconds, and then Henrick's voice came back over the com. "You know, I didn't finish telling you about Isako and the groundhog. Every spring and summer she would curse that animal a hundred times over for the damage it did. But one day we found it dead, lying in front of Isako's gardening shed. A dog or something had attacked it. Isako—that was my wife you know—she knelt over the poor thing and cried and cried. Later she buried it in her garden and put a little stone shrine over it. For the rest of her life she planted the grave with phlox, cornflowers, black-eyed susans..." He paused, taking a slow breath. "It's so beautiful here, but it's wrong... it's wasted, it's dead without animals. Do you understand? There ought to be animals here."

  "That's not for us—for you—to decide, Henrick," Ursule said.

  "The dust will decide, but I'm going to do my damndest to convince it. Up to now it's just been reacting conservatively, only thinking about the best, easiest way to protect itself. It doesn't realize what it's giving up, what it's losing. It doesn't know how beautiful this world could be with butterflies, bees, birds, groundhogs..."

  Two hours later, the longboat lifted off. Standing on the edge of a sun-lit prairie, Henrick watched the thread of light and smoke arc up into the sky.

  Time passed.

  One day, in the shallows along the shoreline, a small crustacean-like sea creature found itself stranded on a mudflat by the withdrawing tide. On a nearby rock, a nodule of dust began to collect. It stayed there for hours, watching. It watched with some fear, but also with wonder and excitement. It watched until the tide returned and the crustacean was carried back to the safety of the water.

  * * *

  Lighting Up the Brain: The Use of Electromagnetic Radiation to Stimulate Neurons

  Science Fact Kyle Kirkland | 5597 words

  We've learned to do a lot of things with light, or more generally, electromagnetic radiation. The spectrum of electromagnetic radiation runs from low-frequency radio waves up to high-frequency gamma rays, with visible light somewhere in the middle. Radiation is used in transmission, medical imaging, solar energy conversion, lasers, and so on. But stimulating the brain? That's probably not an application of light 1 that you'd think of. There would appear to be some serious obstacles.

  For one thing, the skull is in the way, and it doesn't exactly let the sun shine in. Another thing: do neurons respond to electromagnetic radiation? You wouldn't think they'd have much of a tendency to do so, given the skull's lack of transparency.

  These are important issues, but they're solvable if you really want to use radiation to stimulate the brain. The skull is opaque to visible light but some frequencies of electromagnetic radiation can penetrate it to at least a certain extent. Or if you're determined to let in a little more light, a craniotomy—making a hole in the skull—is an option.

  Finding organic molecules that react with light isn't hard either. For example, plants use chlorophyll in the process of transforming solar energy into chemical energy stored in carbohydrates. The mammalian nervous system provides another example: cells in the retina called photoreceptors contain molecules that convert light into electrical signals, which are then conveyed to the brain. These retinal molecules that react to light belong to a class of substances called opsins. One type— rhodopsin—is extremely sensitive to light and is the basis for our night vision. Other kinds of opsins include three that are tuned to different wavelengths—red, green, and blue to a rough approximation—and provide color vision.

  Neuroscientists have recently devised two new but entirely different research techniques that employ radiation. One method involves incorporating photoreactive molecules into neurons, a process that allows researchers to turn a neuron on or off with the flip of a light switch. Another method uses a type of radiation that penetrates the skull and is scattered by the brain, providing researchers with a new and inexpensive way of imaging neural activity without having to open up the skull. 2

  These techniques are interesting and I'll briefly describe them below. But what really fascinates me is how these techniques could be extended and combined in the future to create a brain stimulator with an incredible number of possible applications. This is pure speculation on my part, but I think it's doable, and it's something that can transform lives without any drastic and risky operations involving craniotomies. It might even be done stealthily, which leads to questions about who might be transforming whom—and for what purpose.

  First I'll discuss the science, then the speculation. One of the new research techniques that uses radiation in a novel way is a marriage of fiber optics and DNA transfer called optogenetics.

  Optogenetics

  Neuroscientists have long wanted to have the ability to stimulate or manipulate the activity of specific neurons. You can do this in vitro, but neurons sprawled on a dish don't always tell you a lot about the functions of networks in an intact, living brain. For in vivo experiments, the conventional method of stimulation involves the insertion of little metal electrodes into the brain. But this isn't a very precise method. Even if you use a tiny pair of wires insulated everywhere except the tips, the current flows through a relatively large region and you can't control where it goes. You can certainly stimulate the brain with these electrodes—and researchers have been doing it for decades in experimental animals as well as a few human patients—but since you're not exactly sure what you've stimulated, it's often difficult to interpret the results. To stimulate individual neurons you need to poke a tiny hollow electrode through the cell's membrane. This is relatively simple to do to neurons in a dish, but it's much more diff icult to do in an intact brain—and you can't see or aim at what you're trying to hit. You can use a microscope to examine neurons in a dish but with an intact, living, pulsating brain you just have to sink the electrode into the tissue and hope for the best.

  To do better, you've got to make the targeted neuron or neurons stand out somehow, or make them more susceptible to the method of stimulation. Optogenetics makes them more susceptible. You insert genes into the targets that will make them responsive to radiation, then shine a light on the general area. You don't have to pick out the neurons because they're the only ones in the bunch that will "notice" the light.

  I'm not going to describe the methods of gene transfer and DNA technologies and such—people have been doing these things since the 1970s. But optogenetics didn't really get going until scientists discovered some interesting opsins in microorganisms that control the flow of current across membranes. They are similar to ion channels, which are crucial proteins in neurons that form little pores in the membrane for charged particles to pass through. (Cell membranes are otherwise impermeable to ions.) Most of the ion channels normally found in neurons are opened and closed by one of two different gating mechanisms: the binding of a certain molecule gates some kinds of channels, and a change in voltage across the membrane gates others. But the channels that scientists found in microorganisms are gated by light. If you insert the gene that codes for
one of these channels, such as one called channel-rhodopsin, then you've got a neuron in which you can induce a current just by shining a light on it.

  Sounds easy, but it took a lot of time and effort to get this technique to work. You can't simply plug a gene from a microbe into a mammalian neuron and expect the protein that the gene encodes to get synthesized and function correctly. Karl Deisseroth at Stanford University and his colleagues pioneered many of the techniques currently used in optogenetics, and began publishing their findings in 2005.

  To get the gene into the neurons, scientists often use viruses that reproduce by invading cells and inserting their genetic material into the cells' DNA. But the viruses are altered so that they insert the opsin gene along with regulatory sequences that don't allow the gene to be activated, except in certain types of cells. For example, the gene may be active only in neurons that use a certain kind of signaling molecule, such as dopamine. Such neurons are often involved in processing certain kinds of information, such as reward and reinforcement or the coordination of voluntary movement. So although the virus infects a lot of cells, only a targeted subset of neurons actually express the gene (i.e., make the protein that the gene encodes). You can also use transgenic techniques—cloning and breeding—to introduce the gene into neurons, but this process takes a lot longer. 3

  The brain needs to be exposed to light before it can be stimulated optically, so researchers have to perform a craniotomy (the process of injecting the virus may also require exposing brain tissue). Fiber optics can deliver light pulses as needed, onto the surface as well as deep in the brain. A nice bonus with this method is that the optical stimulation doesn't interfere with electrical recording devices, so you can monitor neural activity while you stimulate the targeted neurons. This can easily be done on an anesthetized animal, and also on an awake, mobile animal, though it poses certain challenges, especially if the animal is as small as a mouse. But Polina Anikeeva, Karl Deisseroth and their colleagues have developed an "optetrode" that can record and stimulate from multiple channels in freely moving mice. 4

  You can also conduct optogenetic experiments in vitro. Jan Tønnesen, Karl Deisseroth, and their colleagues recently studied the behavior of grafts of dopaminergic neurons (neurons that use dopamine) derived from stem cells. 5 In Parkinson's disease, dopaminergic neurons die in a specific region of the brain, and physicians are trying to develop a way of replacing them. Tønnesen and colleagues used optogenetics to show that neuron grafts become functional and are incorporated into tissue slices that have conditions resembling Parkinson's disease.

  Near Infrared Imaging

  In the 1990s researchers began using radiation in the near infrared portion of the spectrum to image the brain. "Near infrared" refers to wavelengths that are near red light, which has the longest wavelength in the visible spectrum. Certain wavelengths of near infrared partially penetrate the scalp and skull, and are absorbed or scattered by the outer surface of the brain; the spectrum of the scattered radiation carries information about blood flow and oxygenation. Thus it is a way of measuring brain metabolism, which is an indirect measure of neural activity. Toshinori Kato and colleagues were among the first researchers to develop this technique, as reported in a 1993 paper. 6

  Perhaps the main advantage of this technique over functional magnetic resonance imaging and positron emission tomography is that it's super cheap. Another important factor is that, unlike the other imaging methods, patients don't have to sit still during near infrared imaging. This has enormous benefits when your patient happens to be a toddler who squirms around in an MRI machine like a hooked worm. But there are also serious disadvantages. Brain tissue absorbs near infrared quite readily, so the radiation doesn't penetrate much farther than the outermost layers, called the cerebral cortex. You can't image anything buried deep in the brain with near infrared.

  The near infrared window has a wavelength centering around eight hundred nanometers, give or take a few hundred nanometers. It's strange that this radiation could penetrate very far into tissue, but it makes sense if you consider how much more transparent the body is to red light than violet light (violet is at the high-frequency end of the visible light spectrum). Try this experiment: take a flashlight into a dark room and shine the beam through your fingertips. What color of light seeps through? It looks pretty red to me. Which means much more of the other wavelengths got filtered out.

  So you can shine a light through an intact skull and at least some of the radiation reaches the cortex. And there exists molecules that can make neurons react strongly to radiation, as in optogenetics. Putting both of these concepts together gives me an idea....

  Brain Activation by Stealthy Stimulation

  How could you stimulate someone's brain without their knowledge? I've always wondered if this was possible. Not because I want this sort of thing to happen, but rather because I'm afraid it might. With so much propaganda flooding in from the television and Internet and print media—often masquerading as "news"—I worry about how far some people will go to influence public opinion. Call me paranoid, but it seems to me we're living in a highly manipulative society.

  Until recently I wasn't too worried. The brain is extremely complicated, and in my opinion any kind of simple form of manipulation is sure to fail. It's not like the brain is a uniform glob of neurons that all work the same way and perform the same function. If that were true then maybe you can run a current through the whole brain and control its various activities. But if the brain were that simple, neuroscientists would have figured out how it works a long time ago, instead of merely the incremental progress they've been making the past few hundred years. In reality, the brain is composed of intricate networks and separate systems that perform specific functions and somehow work together to produce our mysteriously unified conscious perceptions.

  This complexity will foil any crude attempt to influence a person's thoughts or behavior by stimulating the whole brain or any large region of it. Such nonspecific stimulation would be like throwing a wrench into an intricate machine and expecting it to fine-tune the operation. All you'll manage to do is gum things up, and that's what would happen to people if you were to stimulate all or most of their brain—confusion. 7

  I don't believe any of the stories of brainwashing, either, and for the same reason—a lack of specificity. Drugs or hypnosis can't get at the brain's subsystems without interfering with a lot of other activity, so the effects will be general. (Drugs could potentially be highly specific, but at the present time none of them are free of side effects.) If you want to control someone's behavior, you'll have to rely on old-fashioned indoctrination and deprivation—fill someone's head full of lies and deprive them of any opportunity to talk to people who might contradict you.

  I previously assumed you couldn't even successfully inf luence behavior covertly, much less control it, with brain stimulation. But now—or perhaps in the near future— there might be a subtle form of brain stimulation that could work. I think of it as a kind of mind nudge.

  First you have to deliver the stimulation to the brain. If you're going to do this stealthily you won't be performing any craniotomies, so you'll have to rely on something that penetrates the skull—a field of some kind, either static or propagating (i.e., radiation). Let's keep the discussion simple and concentrate on radiation.

  Radio waves and x-rays can penetrate biological tissue easily, but energy is proportional to frequency. Radio waves don't have enough energy, and x-rays have too much— radio waves are largely ineffective and x-rays are so strong they ionize molecules (strip electric charges from them) and cause damage if used excessively (and besides that, x-rays are diff icult to generate and control). Near infrared is okay, though not great since it can't get much beneath the cortex, but unless somebody discovers something better it's the best option.

  In some cases infrared radiation alone can cause cells to become active. Vanderbilt University researcher Anita Mahadevan-Jansen and her colleagues have used infrare
d to stimulate peripheral nerves and even neurons in the central nervous system, presumably due to heating. 8 But the responses are mild, so you need something more powerful. And more specific, since this appears to be a general effect.

  To target specific neural systems you've got to make them more susceptible to the stimulation. This is the job of substances such as opsins that react to electromagnetic radiation of certain frequencies.

  But how do you introduce these substances into the brain and get them in the right places? That could be a big problem.

  Optogenetics techniques make use of the body's genetic machinery. This is possible because the substances that researchers want to insert into neurons are proteins, so it's a great idea to use the DNA code—the gene—along with regulatory sequences that can be targeted to a specific group of neurons. When you're dealing with experimental animals you can inject the viral carriers directly into the brain, or you can develop a line of genetically altered animals. Neither are particularly viable options if your goal is to secretly stimulate a person.

  But viruses are sneaky. A number of viruses can slip into the brain through various (and generally not well understood) tricks—rabies, herpes simplex, and HIV are examples. If you gut one of these viruses and outfit it with the right sequences, perhaps it could work—assuming the molecule you need to introduce into the brain is a protein. (Or RNA molecule, which genes can also encode. But RNA molecules generally don't have the same kind of functionality as proteins.)

  Maybe the photoreactive substance you want to get into the brain isn't a protein but rather some kind of chemical you concocted in a lab. If you want to introduce this substance into someone's brain, you've got an obstacle—it's called the blood-brain barrier. The blood-brain barrier is a web of cells and membranes that filter the brain's blood supply. Nutrients slip in, but not large molecules. It generally does a good job of keeping the brain's environment relatively free of potentially irritating substances floating around in the blood vessels. It's also the bane of neuropharmacologists.