Kraken

by Wendy Williams

  But there is one very special group of animals that turns out to have a very thick axon: squid, including little Loligo pealei. This tiny animal, which Bruce Andersen held in his hand that rainy November afternoon, is only a few inches in length. Yet it possesses a “giant axon,” that, if you look carefully, is visible to the naked human eye. Little Loligo’s giant axon is not particularly long, but it is very thick. It’s sometimes said to be “as thick as a pencil lead,” but most specimens are not. However, many are about a thousand times thicker than a human axon.

  A handful of little Loligos

  Loligo’s axon evolved in order to protect the animal from predators. Squid are among the fastest swimmers in the sea, and the purpose of this very thick axon—also possessed by Dosidicus—is to help the squid jet away from danger at lightning speed. Most of us cannot send messages to our arms and legs with anything like the speed of this little squid, although I did that day see Bruce Andersen, after several tries, catch a Loligo in a tank with his bare hands. His feat was quite impressive.

  For obvious reasons, this thick axon is much easier to study than a human axon. If you are highly skilled—and even neurosurgeons with their super-steady hands need to practice this delicate task—you can remove this axon from the squid and insert tools in it to discover what’s going on inside.

  This is fortuitous. But what’s equally as convenient is that these small animals are abundant. It’s not so easy to find a giant squid, but at the right time of year—spring and summer around Woods Hole, as it happens—Loligo pealei are as thick as gnats. Traveling only a few miles away from home port, Cape Cod fishermen catch them by the boatload, either to sell to a fish market to be turned into calamari, to use as fish bait, or to send to a research lab for study.

  CHAPTER EIGHT

  SOLVING FRANKENSTEIN’S MYSTERY

  It’s the squid they really ought to give the Nobel Prize to. . . .

  —ALAN HODGKIN, NOBEL LAUREATE

  n the streets of Woods Hole, there’s a fellowship of souls in the peaceful hour of darkness before dawn. “Mornin’” is the preferred greeting at this special hour, along with a polite but reserved acknowledging nod when two bodies pass each other. There’s a sense of community. Most of the people up at this hour are finishing their caffeine and heading out on the water.

  One promising August morning in 2009, squid lover Joe DeGiorgis, professor of neuroscience at Providence College and a Marine Biological Laboratory researcher who studies the inner workings of the squid axon, was carrying enough coffee and pastry to keep the crew of the fishing boat Gemma well buzzed for hours. Joe was looking forward to a fruitful trip. The Gemma looks quite like any of the Cape’s fleet of commercial fishing trawlers, but it’s actually the collecting boat for the Marine Biological Laboratory. For decades, the Gemma has gone out most summer mornings with the first raising of the Water Street drawbridge. The mission: collect enough squid, clams, sea urchins, monkfish, and whatever other marine animals are needed to fill the day’s research needs of the institution’s scientists.

  For Joe, this particular morning was a kind of homecoming, since he’d started his career at MBL as a collecting diver whose job was to hunt for animals like the sea urchin and the common surf clam. Along with the cephalopods, these sea animals, like so many other sea species, have contributed greatly to medical research. Both the sea urchin and the surf clam are extremely practical as research specimens, since they are abundant and easy to harvest, and consequently, cheap.

  Various sea species have specific qualities that make medical research easier. The eggs of sea urchins, for example are large and develop quickly. They’re also transparent, so that, unlike in a hen’s egg, for example, scientists can watch the process of the animal growing and developing inside the egg.

  Victorian scientists used sea urchin eggs to learn about human fetal development. In 1899, MBL summer scientist Jacques Loeb made an important discovery: He could get unfertilized sea urchin eggs to divide and form new animals by putting the eggs in certain kinds of liquids. The ease of initiating the development process meant that researchers could—and did—make astounding progress in understanding this very early stage of the development of a living organism.

  Surf clams, the diced-up bits of flesh you’re probably eating when your dip your spoon into a bowl of clam chowder, have also contributed to the progress of human medicine. Surf clams are mollusks, like squid, but much less complicated. The surf clam’s life consists mostly of hiding in its shell, buried deep in the sand, sucking water in and filtering out whatever nourishment is around.

  While Joe was a diver, scientists were using surf clams and sea urchins to do basic research that ultimately ended up improving cancer treatments.

  Almost all cells in the human body divide into two, then regrow. This is why skin heals, fingernails grow, and hair gets long. Growing new cells is an essential process: Out with the old, bring in the new. But the body usually controls that process very carefully. Under normal circumstances, the cell divides only after a certain time period.

  Promiscuous activity resulting in lots of cell division is unwelcome. Cells are not supposed to keep dividing. Various types of cells in your body routinely divide at different rates, but most of the new cells are supposed to undergo a kind of rest period, before they wear out and are cast off. A cancer occurs when the cells continue to divide and divide, never taking time to relax and just smell the roses.

  To better understand why some cells become cancerous, researchers need to better understand the basic biology of cells. What makes normal cells divide in the first place? Without understanding the normal process, it’s harder to control the abnormal process. Using some of the species of animals collected by Joe, researchers learned that two different complex molecules in a cell—called “cyclin” and “ubiquitin”—control the basic divide-then-rest routine.

  Cyclin and ubiquitin are a yin-and-yang pair. They work as a duo, balancing each other out in a wonderful example of teamwork. Cyclin builds up over the life of a cell, then, when the correct time comes, the ubiquitin attacks the cyclin. It breaks up the complicated molecule so that when the cell divides, the new cells don’t have as much. Then the cycle of buildup and breakdown begins anew in the just-divided cells.

  Nature is often organized in this pleasantly logical way. The compound cyclin was discovered by MBL summer scientist Tim Hunt of Great Britain in 1982, while he was studying sea urchins. Hunt learned that the amount of cyclin in a cell increases gradually over the life of that cell. Finally, it reaches a peak. The peak is the signal for action. The cell divides. For finding this clue in the mystery of why cells divide, which provided a completely new strategy for treating cancer, Hunt and several colleagues won a Nobel Prize in 2001. Later, Joan Ruderman, one of the students who worked with Hunt in 1982, found that some breast cancer cells do indeed have too much cyclin, which could possibly initiate too much cell division.

  The discovery of ubiquitin came around the same time. Ubiquitin is so named because it is ubiquitous—present, like cyclin, in nearly all animal cells, even in tiny algae. It is ubiquitin that destroys cyclin so that the new cells don’t have too much. What goes up must come down. If the amount of cyclin were high in the new cells, the cells would keep dividing. Ubiquitin ensures that this doesn’t occur by breaking apart the cyclin, so that the healthy, well-measured dividing of cell growth can begin again. The discovery of ubiquitin earned MBL summer researcher Avram Hershko (who, as a six-year-old, narrowly escaped an Auschwitz gas chamber) and several other colleagues the Nobel Prize in 2004.

  One of the most marvelous things about cyclin and ubiquitin is that these molecules are present in almost all living cells—in plants, in yeasts, in most animals, and in humans. Across all these species, the compounds are similar enough that scientists believe they must have been present in very early life-forms. In scientific jargon, the genetic recipes for these molecules have been “conserved” throughout much of evolution.


  While Joe was diving for research purposes, he began to learn about the natural behavior of squid. He learned that Loligo pealei has elaborate courtship behaviors, and that when a male mates with a female, he sticks around afterward, trying to keep the other males away.

  “It’s like a bar scene, when a guy has one eye on his girlfriend and another on every other guy in the room,” Joe explained.

  When the first female of a shoal of squid lays her eggs, the second comes along and lays her eggs in the same place. The second female attaches her eggs to the first batch of eggs, and so on and so forth, until all the females have left their gifts to the sea. “It finally looks like a huge anemone,” Joe said. “There are hundreds of fingers, all containing eggs, physically linked together. It’s an event. They reproduce as an event.” From then on, the development of the baby squid is synchronous. They develop together, watching with their eyes all the others in their group. They hatch together. They school together, swimming as a group throughout their very short life span (less than a year). Thus, one shoal of hundreds of squid may go through a complete life cycle together, as though, in some ways, they are one living being.

  Joe was also fascinated by the braininess of the little animals. “Besides the fact that they’re very beautiful, they’re very intelligent,” he said. “The point is—they’re thinking. Does a mouse think on their level? Probably not. Does a dog? Depends on the dog.”

  For a while Vineyard Sound Loligo were in great demand in laboratories around the world. Joe started a business called Calamari Inc. Laboratories put in their orders for a variety of squid parts—eyes and axons and fin nerves and brains—and Joe would dissect the squid and send the scientists what they needed. A scientist from the National Institutes of Health called him one day and asked for 2,000 squid eyes. The scientist was studying how eyes actually see. Joe sat down and removed squid eyes, one every five minutes at $5.00 an eye, froze them, and sent them to Washington.

  At $5.00 an eye and twelve eyes an hour, Joe was making pretty good money for a kid. But he eventually realized he was bored sitting on the sidelines. He was interested in the neuroscience itself. He went on to earn a doctorate in neurobiology. These days, he heads his own MBL lab, and is working on squid science that he hopes will help lead toward a cure for Alzheimer’s disease.

  But he’s always happy for a chance to ride on the Gemma. As we crossed the Sound that August morning, basking in the early morning sun, we headed for a prime fishing spot near the island of Martha’s Vineyard. I asked DeGiorgis about his most unusual dive in these waters when he was still working for the collections department. He said it was the sudden appearance one day of hundreds and hundreds of salps, strange jellyfish-like organisms that make long chains and float through the water, eating and growing along the way. On that particular dive, he had to part the strands as he moved through the water. “It was like walking through a beaded curtain,” he said. “It was a virtual sea of salps. Then, the next day, they were all gone. Vanished. It was a place where I’ve dived more than anywhere else in the world. I’ve never seen them again. Bizarre.”

  Joe DeGiorgis dissecting a squid

  The squid fishing wasn’t great that warm late-summer day, but after a series of runs with the trawling nets, the crew had brought up enough Loligo pealei to call it a day. Back at the dock, scientists and their lab assistants dropped by to pick up their orders for another day of research.

  After the trip, Joe dissected an axon to show how it’s done.

  “The neuron is shaped like a tree,” he explained later. “It has ‘branches’—the dendrites; a ‘trunk’—the axon; and ‘roots’—the terminal end of the axon. The axon, the trunk of the tree, is what I’m interested in.”

  He tied off both ends of the axon using thread, black on one end and white on the other, like you might tie the end of a balloon. Then he gently lifted the axon out of the squid’s body and placed it on a petri dish. He peeled away the unnecessary tissue clinging stubbornly to the outside of the axon. It was kind of like peeling a banana. That left the naked axon, containing only the goo—the “axoplasm”—that filled up the axon’s insides.

  It took him about five minutes. In Joe’s experienced hands, the task looked easy.

  To prove the axon was still doing its job, he put an electrode inside it.

  The clicking sound, the buzz of electricity, was clear as a bell.

  As nerves, bundles of axons produce the river of power that runs through your body. Electricity, the same physical force that turns on your electric lights or makes your computer work, is the force that enables you to think and dream and play baseball and drive a car. That’s why many medical textbooks equate the nervous system to a system of electrical wiring. “Life exists because of a delicate dance of electrons,” wrote author Joseph MacInnis. Without Loligo pealei, we might not have several basic facts that led us to this understanding.

  For thousands of years, we’ve known that some sea animals produce electric shocks. Torpedo rays, capable of stunning their victims with as much as 220 volts of electricity, found their way into Plato’s Dialogues. Early Roman physicians used these animal-generated electric shocks to treat human ailments like headaches and gout, presumably with some success. But while ancient cultures understood that some animals were capable of emitting shocking levels of electricity, they did not understand that all muscles—including our own—contain and discharge electricity.

  The fact that our muscles work because of electricity was discovered around the time of the American Revolution. Other scientists had played around with the phenomenon of electrical interaction with animal muscle, but it was Italian scientist Luigi Galvani who did the first series of solid experiments in the field, in the 1780s. During a storm, Galvani saw that a severed frog’s leg, hung outside on a copper hook on an iron balcony, twitched when lightning appeared in the sky. He also found that he could make the severed leg twitch with static electricity, as well as when he sent electric current from a Leyden jar, a kind of very primitive battery, into the dead leg. He thought about this a great deal and finally suggested that the muscles themselves created their own unique kind of electricity, which he called “animal electricity.”

  While Galvani was studying “animal electricity,” other scientists were independently studying electricity more generally. Ben Franklin, of course, established that lightning bolts were bolts of electricity, and also coined many of today’s basic electrical terms, like “positive,” “negative,” and “current.” The impish Franklin liked to show off for his dinner guests by killing turkeys with bolts of static electricity.

  Franklin and other researchers imagined that electricity was rather like water, only invisible. Yet while Franklin and others were able to work out a bit about what electricity did, they did not understand why electrical phenomena occurred. The discovery of what was actually flowing—energy from the bouncing around of negatively charged electrons—would not occur for another century.

  At first glance, the discoveries of Galvani and Franklin and many other scientists seemed contradictory. Too much electricity could, obviously, kill. On the other hand, a jolt of electricity seemed, from Galvani’s experiments with frogs, to give life. How could this be?

  Scientists proposed the existence of two different kinds of electricity and suggested that the electricity in a frog’s muscle differed in some basic way from the electricity Franklin discovered. The electricity that moved muscles became “animal electricity.” Franklin’s lightning-bolt electricity became “natural electricity.”

  This may seem silly to us today, but then many scientists thought it reasonable. After all, how could bolts of static electricity kill a turkey but also, apparently, give life to a dead frog’s leg? The whole thing seemed very odd.

  The public was both confused and fascinated. An “electrical frenzy” swept Europe, writes neuroscientist and historian Stanley Finger. For much of the nineteenth century, people imagined that electricity could do all kinds of things.
Percy Shelley, the great English poet, tried to cure his sister’s skin disease by using electrical shocks and, explained Finger, “managed to electrocute the family cat in the process.”

  Smatterings of what the scientists had learned gradually entered the popular culture. The verb “to galvanize” entered the vernacular, and some people claimed to be able to use electricity to encourage people to become more active. (And indeed, it does turn out that when you administer an electric shock to someone, you do “galvanize” them into action.) Other people began to wonder if the electrical force wasn’t what created the human “spirit,” which seemed to disappear when a person died. Could you use electricity to bring back the dead?

  As often happens, this scientific breakthrough caused a popular uproar. To many people, it seemed as though scientists were eating apples from the Garden of Eden, usurping knowledge and abilities that should belong only to God. And thus was born Frankenstein; or, The Modern Prometheus, perhaps the first-ever novel to be written in the mad scientist genre. Mary Shelley, a bored English teenager, was hanging around the resort of Lake Geneva with friends, including the poet Lord Byron and her lover, Percy Shelley, in the extremely cold and very rainy summer of 1816. Because of the weather, Mary and her companions were stuck inside, forced to huddle around a warm fireplace, swaddled in layers of clothing.

  On one of those chilly evenings, Mary listened to Percy and Lord Byron explore the essence of the word “galvanize.” Was it really possible, they wondered, to assemble body parts and create a living being? Would it ever be possible to discover “the nature of the principle of life”? In Mary’s fertile imagination then appeared the fictional character Frankenstein, a scientist who did just that. In her novel, after building the technology and assembling the body parts, the professor brought to life a humanlike monster. “It was on a dreary night in November,” Mary wrote in chapter five, “I collected the instruments of life around me, that I might infuse a spark of being into the lifeless thing that lay at my feet.” Powered by electrical shocks, the monster opened its dull yellow eyes, breathed, and began to move its muscles.