In the first few weeks, using a time-honored sophisticated technique of neurophysiologists, they squished the axons to squeeze out the axoplasmic goop inside. They didn’t find many of the atom-huge sodium ions there, which was intriguing, since there are plenty of sodium ions in seawater and in blood; sodium, after all, is just part of ordinary salt (sodium chloride). The salty taste of seawater or blood, be it squid blood or human blood, is a sign of those ions in operation. Something inside the membrane of the squid’s axon was taking sodium ions, those huge modified atoms, and grabbing on to them, and pushing them right through the membrane, so that they built up on the outside of the nerve.
This was great; this was seeing details that the German researchers of the 1860s had only guessed at. The squid was stockpiling sodium ions outside the membrane of its nerve cells. But, why? The two young men had a hunch—they’d studied physiology at Cambridge with the world’s experts—but before they could go any further, the war came. Hodgkin worked on radar, Huxley with the Admiralty, and it wasn’t until 1947 that they could get back to full-time research. Hodgkin’s new wife, Marni, wrote to her parents:
“Alan…is like a dolphin that has suddenly been released….He plunges and gambols and cavorts in pure research after so long….”
It was frustrating to have stopped, but the years in radar hadn’t been wasted. Hodgkin and his wartime colleagues had repeatedly used the old insight that it’s easy for electric currents to travel along a smooth, wide path. There are usually plenty of available electrons in such a big path, and so there’s not much “resistance” in the way. Narrow paths, however, are harder for electric currents to continue along. The electric current faces more resistance. Since most nerves are very narrow (notwithstanding the relatively enormous nerve of a squid), they offer immense resistance to any electricity trying to squeeze through. This means, as Hodgkin explained a little later:
“If an electrical engineer were to look at the nervous system he would see that signalling electrical information along [narrow] nerve fibres is a formidable problem….The [nerve] fibre is so small that…the electrical resistance of a metre’s length of small nerve fiber is about the same as that of 10,000,000,000 miles of [thicker] copper wire, the distance being roughly ten times that between the earth and the planet Saturn.
“An electrical engineer would find himself in great difficulties if he were asked to wire up the solar system using ordinary cables.”
Nerves have to work differently. They can’t pour their electricity straight down the middle of their axons, as Alexander Bell had imagined electric sparks rolling down a copper wire in his telephone. Instead, nerves have somehow to be powered up from the side, getting regular boosts from something very strong and stable waiting here. It would be as if an engineer knew he or she was going to have problems keeping a signal going in a long wire, and so thoughtfully installed, oh, a few trillion booster units at regular intervals along the edge.
That’s what the huge sodium ions were doing. They were there to keep a nerve signal going. (Further research showed that potassium ions are also central to nerve conduction, but since their operation is similar, the text will stick to sodium for clarity.) When we have a thought, and a nerve cell in our brain begins to fire, the signal will die out in a fraction of a millimeter unless some of this charged-up sodium squeezes back in from outside to keep it powered along. What Hodgkin and Huxley made clear—and what earned them a Nobel Prize—was that the cell membrane isn’t a continuous rubbery barrier, impermeable and secretive, keeping our thoughts locked in coy Freudian depths. Rather it has lots of little gaps that widen to let the sodium ions go through. Not a lot has to pour across, just a few thousand sodium ions along any millimeter of the nerve, but that’s enough.
Anything that lets the sodium boosters in will start a signal. In an eye peering at a computer monitor, for example, the incoming electric waves from the screen hit ingeniously shaped molecules known as rhodopsin, which exist on the retina. Imagine the rhodopsin molecules as palm trees. The molecules twist like palm fronds in a typhoon when the light hits, and a part of the rhodopsin—its “roots”—pull upward. Since the rhodopsin trees stand in a slurry of sodium ions, gaps open at the base of each one as the trees lift up. The sodium pours through those new gaps into the nerve beneath, and the signal begins.
That first jolt of sodium, entering the very start of the nerve, makes the next millimeter of nerve membrane do something strange. It warps and bubbles and contorts and then, suddenly, holes start opening up there, letting more sodium that’s been waiting farther along on the outside pour in. When that booster sodium arrives, the next section of the nerve has the strength to bubble with opening holes. Sodium that’s been stored on the outside even farther along pours in, and the sequence repeats, rippling quickly along the full length of the nerve.
After the whole signal has traveled along, the nerve is a bedraggled mess, pierced with holes and sloshing with sodium. Before it can fire again, it has to rebuild itself, which means bailing out the extra sodium that poured inside, and closing up the holes. That’s so energy-consuming, as is keeping the electrified sodium on the outside, and not letting it dribble in while waiting for another signal, that 80 percent of the energy that goes to our brain—all the sugar and oxygen; all the nutritious residue of steaks and muesli and Frosted Flakes and Junior Mints—is devoted simply to fixing this sodium-hole damage.
Sometimes the nerve doesn’t recover as quickly as usual. When the air is cold, your fingers get clumsy. That’s because the fatty nerve coverings in your fingers start to thicken, much as greasy lamb’s fat congeals after a meal. As a result, the sodium pumps within the nerves that go to your fingertips don’t work as well as they do in warm weather. It’s why we need to warm up before any task that requires fine motor control. Glenn Gould, the great pianist, was often restless before playing, until he could find a deep sink or bucket where he could plunge his arms in hot water. Critics sometimes made fun of him, but then they heard the results. Once his congealing fat had softened, once the path for his electric-powering sodium ions was ready, Bach’s masterpieces were his. (Ice cubes help keep down the yelps in earlobe-piercing for the same reason.)
Sometimes the problem is more serious than a gust of chilled air. The liquid called tetrodotoxin is one of the gravest nerve poisons that exist. When it splashes around a nerve, it acts on the sodium pumps, closing them tight. Were this to affect only a few nerves, such as the ones involved with our looking around, befuddled, to find the exact location of the TV remote control, that might not be too bad. But there’s a great similarity in nerves throughout the body. As the tetrodotoxin seeps everywhere, the nerve signals traveling to the heart and lungs are affected as well. We might have some awareness of this, we might look down and quite sincerely want our nerves to keep firing, but with the sodium channels blocked and none of those booster ions falling in, the electrical signal would soon peter out. The result would be death by suffocation. Tetrodotoxin is produced in its natural state by the dreaded Japanese puffer fish and duplicated by eager chemical warfare specialists worldwide.
Alcohol is a bit in-between. It makes the fatty nerve membranes begin to congeal, but not enough for instant death. The result is more like cold-finger fumbling, only this time the membrane disruption operates on nerve cells deep inside the brain, carrying our thoughts and memories, rather than just in the extremities. For those who, as Samuel Johnson observed, wish to escape from themselves, it’s consoling to temporarily weaken the walls that hold their electricity-boosting sodium pumps in place.
Technology regularly advances faster than science, and people happily used alcohol and—if wise—avoided puffer fish, for thousands of years before the details of sodium pumps were known. Early anesthetics were similar. They were greatly needed, for alcohol barely works in stopping surgical pain, and even into the mid-1800s the big teaching hospitals had to employ burly “grippers,” such as ex-stevedores or boxers, whose job was to stride after esc
aping surgical patients and drag them back to the operating theater for their ordeal. (Flaubert, son of a surgeon from this pre-anesthetics era, gruesomely described what surgery then meant in the leg-amputation scene in Madame Bovary.)
The change with anesthetics came in the early and mid-1800s, when various helpful gases, such as ether, were found to knock out patients without too much fatality. Sigmund Freud, as a young medical student in the 1880s, was especially fond of experimenting with the properties of the modified plant extract called cocaine. It was excellent for eye operations, and also pleasing for the surgeons who sampled it, often repeatedly, just to confirm that the doses were right.
Only with the work of Hodgkin and Huxley was it clear, though, how anesthetics might work. Much as with alcohol, many of these molecules sink into the fatty membranes of our nerves, and diminish the working of ion pumps along nerve axons wherever they arrive. Pliers might be savagely tugging at a molar, or a needle might stitch together pieces of living tissue, but the nerve impulses with which the brain would recognize these iniquities will advance barely a fraction of an inch before—sodium boosters off—they dribble to a halt. As the details of how they work became known—and the different modes of action of general versus local anesthetics became clear—medicine improved tremendously. Serious operations such as heart bypasses became possible; keyhole surgery on knees became possible to control. Victorian engineers had only big electric engines and used them to move elevators or to run machine tools or refrigerator pumps. Today’s biological engineers can use the microscopic electrical pumps of sodium ions to control far more delicate maneuvers within.
Hodgkin never got around to inebriating his squids, but colleagues did ply them with tetrodotoxin (which sounds unkind, but, given that the nerves being used had been removed from the squid’s body, the objection is perhaps moot). When they poured tetrodotoxin directly on nerves to stop the sodium entirely, and then watched as it wore off, they could see exactly how the sodium pumps began to operate again. What they discovered was humbling to anyone who takes pride in our distance from tentacled, wide-eyed marine creatures. The mechanism was exactly the same as in humans.
“Considering,” Hodgkin said, “that the squid is a very distant relative of man—our last common ancestor…died several hundred million years ago—this similarity in behaviour points to the survival value of the sodium channel in the animal kingdom.” There is a sensible logic here, for living organisms—humanoid or cephalopod—have no choice in what materials to work with. Ions are an excellent, jury-rigged way of using electric current to send signals. What worked in the year 300 million B.C. holds up today.
12
Electric Moods
INDIANAPOLIS, 1972, AND TODAY
For all those hundreds of millions of years, electrically thinking life-forms have wriggled, run, slept, procrastinated, or otherwise occupied themselves on our planet. Within each of these creatures, electric signals have been shooting along membraned nerve tunnels, like the world’s most intricate roller coaster, its cars all lit up and racing along at night.
But in time each signal reaches the end of its nerve fiber. This presents a problem, for nerves don’t form a giant tube network, plugging continuously from one into the other. Instead there’s a gap between any two nerves. This gap, called a synapse (from the Greek word, synaptein, meaning “to fasten together”), was clearly seen as early as 1897. It’s not a very large separation, just a few thousandths of an inch, but on the microscopic level it’s a near-oceanic fissure.
How can the signal cross it? The solution would be the next great step in understanding our nerves and mind. Electrons would be swallowed up in the gap between nerves, and even single ions would be as useless as great beach balls bobbing in a sea. Yet microscopists knew that something had to make it across. They even suspected it was electric. But if it wasn’t a small electron, and it wasn’t a large atom ion, what was it?
The answer came from a forty-seven-year-old man, a pharmacologist at the University of Graz. Late on Easter Eve, 1921, he woke up in the night, suddenly realizing exactly how those gaps are traversed. This was fabulous; science’s understanding of the nervous system would now be complete. He switched on the light, wrote down his great insight, then fell back asleep. In the morning he woke up again. He’d always been a promising researcher, but what he’d dreamed of that night: well, it was an idea for the ages. He looked at the piece of paper where he’d written his great idea.
And he couldn’t read it. Penmanship had always been one of Otto Loewi’s fortes, but not at three a.m. The next day was one of the worst of his life. However much Loewi stared, he couldn’t make out his scrawled words on the slip of paper he’d used. Nor, however hard he tried, could he recall even a fragment of what he had dreamed.
The following night, Sunday, he delicately let himself fall back asleep. If he was lucky, the answer would come back. Midnight came, he was still asleep—no dream. One a.m.—no dream. Two a.m.—still no dream to wake him. But then, as Loewi lovingly remembered: “at 3 o’clock, the idea returned. It was the design of an experiment.”
This time he wasn’t going to trust his idea to pen and paper. Loewi got dressed and hurried along to his laboratory. He had a way to identify the substance emerging from a nerve! What Loewi realized he had to do—squeamish readers might wish to skip the next few paragraphs—was to kill two frogs and cut out their hearts. He’d keep one heart attached to the nerves that poured their unknown chemicals down on the heart. He’d watch to see how the heart behaved—whether it slowed down or speeded up—as he made more of the chemical come out of the nerves. Then he’d siphon that unknown chemical so it poured over the other heart. If the second heart reacted in the same way, then he’d know that something in that liquid carried the answer.
Loewi could do this, for, like many anatomists of his time, he had a ready supply of unfortunate frogs at hand, and he knew that even a deceased frog’s heart would continue beating for quite a while. He got to work with his scalpel and soon had the two hearts in two separate buckets, where they throbbed away. He squeezed on the big vagus nerve leading to the first frog, so that more of whatever liquid it had inside came out. The first heart slowed down. He then led some of that liquid into the second bucket, where the second heart was still pulsating away, entirely on its own. A few moments after he poured in the liquid, the second heart also began to slow down. The liquid that came out of living nerves really was powerful enough to do that.
What Loewi and his successors realized was that inside these liquids that squirt between our nerve cells there are relatively ponderous floating molecules. They’re often built of several hundred atoms stuck together, making them much bigger than the bobbing sodium ions, so they survive their journey unscathed. They act like miniature submarines. Whole navies of them are released from tiny bubbles in the tip of a firing nerve cell, and they float across the synapse toward their target. Similar molecules exist at nerve junctions throughout the body, and are especially important in the brain’s nerve connections. Since the brain cells we think with are called neurons, these molecules that transmit signals between them are called neurotransmitters. God stretches a forefinger to Adam on the Sistine ceiling, and His nerve endings dribble molecules across which—through the ingenious expedient of opening Adam’s sodium channels—make the first man’s nerves start quivering with electrical surges.
This is how signals cross the gap. Electric signals move along in a nerve to the gap at the end and make a powerful liquid come out of the nerve tip, and that liquid crosses the gap, and enters the next nerve, and carries along the message that the first nerve had sent.
If every one of our nerve cells sprayed out the slow-down liquid Loewi found, however, we’d be in trouble. We’d think a thought, or try to move our arms, and everything would start going slower and slooower and slooooooower. Luckily there are other types of transmitter liquids in our body. Some speed up the cells they reach, while others simply help them form new con
nections—dozens have been found by now. (One of these additional transmitters that Loewi also helped comprehend was initially called Acceleransstuff for its action in speeding up the cells it reached. We call it adrenaline.)
Each of the neurotransmitter submarines has a different shape, and if it finds the right berth for itself, it gets tugged right in. That tug comes from the same sort of static electricity that gives us a shock on a dry day. Several regions on the transmitter molecule have extra negative electric force (from a concentration of electrons there), while matching regions on the target nerve cell have extra positive electric force (from a relative lack of electrons). When the correct two regions get close, it’s as if deckhands were pulling on docking ropes. They snap together tight.
If the process ended there, we’d be in trouble once again. For when the neurotransmitter arrives, the nerve it hits can now start firing, with its sodium pumps opening wide. But if the transmitter remained stuck there headfirst, that firing wouldn’t stop. The signal from the past would keep on recurring. You’d have no way ever to get new sensations from the outside world, nor would you be able to create a new thought. You’d be stuck in that single moment forever.
Luckily there are yet other molecules operating in the gap between nerve cells in our brain and throughout, and their job is to act as demolition crews, disassembling the neurotransmitter almost as soon as it’s made the journey across. In a most convenient burst of ecological efficiency, when they’ve torn apart the transmitter to its constituent parts, they then generally lead those parts back to the original sending nerve, where the parts are reabsorbed, rebuilt, and—all memory of the previous voyage wiped clean—led toward the surface to be ready to be sent out again. Electric forces pull all those parts along. Without that power, none of this would happen.
Electric Universe Page 16