2008 Thesis Excerpts
Singing the Brain Electric
by Grace Chua
In 1999, Mayberg accepted a professorship in neuropsychiatry at the University of Toronto. One of her new colleagues at Toronto was the surgeon Andres Lozano, who had already won acclaim for his deep-brain stimulation operations on Parkinson’s patients. Because Parkinson’s disease has its origins in a clearly defined, well-studied brain circuit, it made an ideal target for deep-brain stimulation.
When parts of the neural network that modulates body movements are hyperactive, their out-of-control buzzing produces the tremors characteristic of Parkinson’s. Removing overactive portions of brain tissue such as the globus pallidus or the subthalamic nucleus seemed to dampen the tremors. But rather than excising brain tissue, Lozano and other neurosurgeons found that deep-brain stimulation – inserting an electrode in the hyperactive tissue and applying current – seemed to have the same effect. What’s more, deep-brain stimulation could be reversed by just switching off the current, which made it somewhat safer than removing a chunk of brain.
Mayberg thought the same approach might work for depression. She knew that the cingulate gyrus, area 25, was implicated in depression. And she knew that other teams were removing tiny parts of the brain around the cingulate gyrus in people with depression, in an operation known as a cingulotomy – and that this surgery seemed to be effective. She and Lozano thought: why not try deep-brain stimulation of area 25 as a substitute for cingulotomies? Would inserting an electrode into area 25 calm it down the way the globus pallidus calmed down in Parkinson’s?
They decided to try it. Starting in 2003, Mayberg, Lozano and their colleagues began to implant electrodes in area 25 in the brains of severely depressed patients. They couldn’t test their procedure on rats or monkeys, because there is no way to accurately simulate depression in an animal. Scientists have created animal models that look a little like depression: rats or monkeys simply give up trying to complete a task under prolonged, chronic stress. But, Mayberg believes, true depression is a uniquely human illness. Hopelessness is one of its symptoms, but in order to be hopeless you need to have the capacity to think about your future, and animals just don’t appear to have that capacity. In order to best help people, Mayberg had to work with people. So Mayberg’s team operated on the most severely ill people, the ones for whom the surgery was an absolute last resort.
The day of the very first surgery, Mayberg was intensely nervous. Even though all her theoretical evidence told her the procedure should work, she didn’t yet fully trust it. She anticipated bad side effects: because area 25 is part of a brain pathway that regulates autonomic functions such as blood pressure and body temperature, she thought that stimulating area 25 might affect those things. In fact, she was so stressed that Lozano had to calm her down. He said, you know more than anyone else in the world about the science behind this. And he asked her, knowing what you do, would you let your mother or sister go through this procedure?
Yes, she said at once. The surgery proceeded.
Sense and Sense-Ability: The Artful Science of Hands-On Medicine
By Allyson Collins
…Taylor has a head start on Ramani, but this does not deter her mission to educate her successors. She arrives at the eighth-floor resident’s lounge at Boston Medical Center with the information for morning rounds: “We have a patient with a good cardiac exam on 6 North, and another gentleman with a lymphatic exam on 7 West,” she reads from scribbles on her makeshift notepad—a napkin. The residents respond excitedly to the lymphatic exam, and file down the stairs. Before entering the patient’s room, they slip on turquoise gauze masks—the man may have tuberculosis. After a few moments of preparation, the nine file inside and begin the medical ritual.
They stand in a semi-circle around the bed with Ramani near the head. With their white coats on and stethoscopes in place around their necks, they take turns introducing themselves to the patient, whose gloomy gaze sweeps the room. As Ramani guides him, the bare-chested man swings his frail legs over the edge of the mattress, sitting up gingerly to leave the bandage under his left armpit undisturbed. He grants permission for the exercise, but sits motionless, hands in fists, fixing his stare downward toward his arms.
“Who would like to start us off?” Ramani asks. “And then we’ll all jump in.” Her coal-colored eyes search for a volunteer to lead the lymph-node exam. Silence. The crowd is hesitant—are they afraid to hurt the patient? Are they uncomfortable with their skills? To ease the tension, Ramani jokes, “Someone once said, ‘The definition of a volunteer is a person who didn’t understand the question.’” They smile, and soon a female resident steps forward.
“I’m not great at this,” the woman begins, but reaches toward him with both hands. She probes his neck with her index and middle fingers. Her circular motions move the skin at one particular position; after a few moments, she shifts her fingers to explore the tissues beneath another section of skin. The lymphatic system helps fight infections as part of the body’s natural immune defenses. Abnormal lymph nodes serve as physical evidence of an infection, though many people have throat problems or allergies that can lead to slightly enlarged lymph nodes. The resident checks for any suspicious changes—tenderness, substantial enlargement (beyond the size of the tip of the pinkie), nodes that aren’t shaped spherically, and nodes that don’t move when prodded. She names each of the glands she detects: the submental, under the chin; the submandibular, below the jaw; the posterior auricular, behind the ear. “Does anyone want to supplement? Add? Subtract?” Ramani asks. They fill in a few additional nodes—upper cervical, supraclavicular—as she draws a diagram of their locations on a piece of paper.
Then, Ramani walks around the bed. “It’s best to examine certain nodes from the back,” she explains, for easier access. She quietly asks the patient to look straight ahead and relax. “I promise I won’t go anywhere near your bandage,” she reassures him as he hesitates. Her dark brown hands prod his long, pale neck. While Ramani explains her maneuvers to the residents and the patient, he sits silently, staring off into space.
After Ramani’s demonstration, the next resident moves into place behind the patient. He begins a bit roughly, applying greater pressure than Ramani, but relaxes in a moment, slowing his movements and feeling more carefully, conscious of each of the different nodes. A minute or so later, another resident takes a turn, closing his eyes as his fingers move gently, lingering on each intricacy below the skin. When he finishes, he pats the patient on the shoulder in silent gratitude. They continue, and this time a female resident’s fingers move gracefully along the neck as if she’s playing the piano, and she verbalizes her thanks. “Are you still doing OK?” the next resident asks as she steps behind him. “It’s like a little massage,” she comments, and at last, he smiles.
He remains quiet, however, as each of the nine scrutinize his “classic findings,” eventually moving downward from the neck to assess the axillary nodes in the armpits. After forty-five minutes, they file out, headed toward the cardiac exam on 6 North, leaving their volunteer to relax.
Air Trade: Promises – and Pitfalls – in the Coming Carbon Market
by Lissa Harris
Right now, grain farmer Dale Enerson of the North Dakota Farmers Union is irritated with the press. In January, Washington Post reporter David Fahrenthold wrote a story about the House of Representatives’ $89,000 stab at achieving carbon-neutrality, in which environmentalists lambasted Congress for paying farmers thousands of dollars to practice farming techniques they would have adopted anyway. “Value Of U.S. House’s Carbon Offsets is Murky,” the headline read.
“That guy. We could tell from the questions he was asking us, he had his mind made up that agricultural offsets were worthless,” he griped. “We got lambasted because we sold 5,000 tons of [carbon offsets]. And we were proud to do it. And we catch hell from the Washington Post , that this was a worthless exercise.”
Long before the Chicago Climate Exchange started, and without any help from carbon financiers, Enerson began adopting no-till farming practices on his 1600-acre farm in Western North Dakota. No-till has long been recognized as an environmentally-friendly practice that helps control erosion and promote soil fertility. It also increases the soil’s capacity to trap and store carbon dioxide from the atmosphere—a fact of soil science that has recently begun to attract attention from folks to whom wheat and corn are bid-ask spreads on a computer screen.
When the U.S. carbon market launches in earnest, Enerson intends to be there. In 2006, he started an offsets trading program for the North Dakota Farmers’ Union. He now heads the offset program for the National Farmers’ Union, which contracts with the Chicago Climate Exchange to provide carbon offsets through no-till, grassland, rangeland and forestry projects.
Every day, Enerson fires up his computer, logs on to the CCX trading site, and makes deals with unseen buyers over the price of thousands of tons of carbon offsets produced by NFU farmers. He’s become something of an armchair speculator, watching the price of offsets pogo up and down in response to the vagaries of the U.S. presidential race. On Super Tuesday, when it became clear that all three front-runners supported cap-and-trade, the CCX traded 1.2 million tons of carbon in a single day.
Not every farmer in the heartland is convinced of the value of changing the way they farm to satisfy the demands of day traders in Chicago, even for pay. Participation in the program is growing, but the payments are still so small that they’re not going to convince many farmers who aren’t already interested in no-till practices to adopt them. That means that, like Enerson, a lot of farmers in the market would have done no-till even without CCX’s help. And that, in turn, means the farmers would probably fail the test of additionality.
“We always get these questions about whether agricultural offsets are additional and whether they’re permanent, and we like to think they meet the test of both,” said Enerson.
But even if the accountants can’t prove his farmers wouldn’t have done no-till anyway, Enerson believes, quibbling about strict measures of additionality for agricultural offsets misses the point. For many critics of offsets, the worry over additionality taps into a kind of visceral disgust for paying people to do nothing. Enerson is getting tired of this kind of criticism. To his view, there’s nothing wrong with a market that rewards farmers for good behavior.
“If I’m storing four-tenths of a ton of carbon dioxide per acre per year, what’s wrong with getting paid for it?” he said. “It’s difficult for people who don’t understand this idea yet—but the whole idea of cap-and-trade puts a value on environmental services.”
Though biofuels scientists like [Tim] Donohue’s group [at the University of Wisconsin] aren’t starting from the beginning, they aren’t many steps into the race, says the DOE’s [Ray] Orbach. It’s frustrating, he says, that far too little research has aimed at the base of biology – truly understanding simple plant genomics, or the mechanics of how proteins work in plant cells. “To me that’s pretty primeval medicine,” he says. “It’s virgin territory.”
Researchers have been trying to break down cellulose for years, but haven’t gotten very far in breeching its defenses. Cellulose isn’t that different from starch, which we eat all the time in staple foods like corn and potatoes. They’re both polysaccharides – compounds formed from many chained molecules of glucose, the simple sugar that ethanol makers want to get at. The difference depends upon how those glucose molecules bond together.
Starch is a straight line chain – alpha linkages, as biochemists call them. They’re weak, which makes starch worthless as a building material and fantastic as a source of carbohydrates for hungry humans. Cellulose, by contrast, has more elaborate beta linkages: thousands of individual glucose molecules join to curl back and wrap around themselves in a web of chemical bonds, giving cellulose a tough, crystalline structure. “That’s why you have wood furniture,” says Michael Ladisch of Purdue University, “not starch furniture.” Humans can’t produce the enzymes in their gut they’d need to digest cellulose, but some other creatures can – cows do, allowing them to graze on grass, and so do insects like termites, which lets them plow through the cellulose in a house’s wooden studs.
The biofuel industry isn’t the first to seek the commercial possibilities of cellulose. Rayon, the fabric made from cellulose, emerged in France more than a century ago, when it was called “artificial silk.” One hundred years ago, in 1908, a Swiss scientist named Jacques E. Brandenberger dreamed up cellophane, the clear waterproof covering. Both of those products take advantage of cellulose’s strength. Nowadays, biofuel scientists want to tear cellulose apart.
Scientists know the basic process they need. Cellulose possesses two layers of defense: its own crystalline structure and its ties to lignins and hemicelluloses, the neighboring polymers in plants that it clings to for strength. So scientists use a two-step process to break it apart. First they crush the biomass and then blast it with steam or boil it in water, breaking the “lignin seal,” as Ladisch calls it – the links to the other polymers. Then they add enzymes to the reaction, proteins that control the speed of chemical reactions. With their help the cellulose breaks apart into sugars, which then can be fermented into alcohol.
Despite this knowledge of the necessary chemistry, as of yet there is no widespread cellulosic ethanol industry. That’s because the best-known process is terribly inefficient. Ladisch, who has been working on this for decades, said the manmade enzymes on the market are still too expensive for large-scale production, and don’t work that well anyway. Plus, piles of money are at stake, so there isn’t a lot of sharing. Iogen, an Ottawa-based biotech company that partners with the Canadian government, is one of the few private firms attempting to make cellulosic ethanol, and a representative absolutely refused to discuss the specifics their process.
The companies and universities that currently produce cellulosic ethanol can produce only small batches despite their huge investment. The BioEnergy Science Center, the DOE-funded group co-led by University of Tennessee agricultural economist Kelly Tiller, plans to build an actual switchgrass biorefinery in addition to their lab work. With some creative design, she said, the plant will have interchangeable parts, so they can install new technology as soon as they dream it up and build it. But when it powers on for the first time next year, she said, researchers will be able to produce about 5 million gallons of ethanol each year. By contrast, the largest corn ethanol plants can produce 100 million gallons or more. “We kind of know how to process starch into sugar,” Donohue says with a bit of nonchalance, “and that’s okay . But we don’t know how to process cellulose into sugars very well – yet.”
Proof Positive: Finding the Cause of AIDS
by Megan Rulison
It is a history packaged in fear and wrapped in controversy. Overnight, scientists were confronted with a deadly disease unlike anything we’d been affected by before. The illness shared none of the familiar hallmarks of past epidemics where cause and effect were often quickly discerned. Rabies results from the bite of a rabid animal and is recognizable by distinctive symptoms of the nervous system, such as paralysis, hallucinations, and fear of water. The cause of malaria was discovered in 1880 when a French army doctor observed parasites in the red blood cells of the sick, and the disease is distinguished by a cyclical pattern of symptoms. But AIDS is a chameleon, disguising itself in many ways. First, the illness begins with rare infections and cancers. So when AIDS was new, a doctor’s first diagnosis was usually some opportunistic illness, not the underlying cause. Second, AIDS has a slow onset; it often takes years to show symptoms, making it hard to pinpoint an exact moment of infection. And finally, when the AIDS outbreak first began, it was not clear how the illness was moving from one person to another. Each of these reasons is used in some form by AIDS denialists today to reject conclusions about AIDS. But in the early 1980s, when the epidemic first began, scientists and doctors confronted the challenges head-on and tracked a virus unlike any before that had infected the human population.
It is 1984, and a short blond woman, her nervous smile peeking from behind a dense gaggle of microphones, clears her throat. As the room quiets, Margaret Heckler, the US Secretary of Health, smiles again and apologizes for her laryngitis. The room is silent except for the rustling of papers; the reporters are not interested in her cough but in what she’s about to say next. But she tries their patience, carrying on through an introduction, building to her climax. Finally, in a hoarse, echoing whisper, Heckler declares, “The probable cause of AIDS has been found.” She continues over the growing murmur, her voice getting stronger with each hopeful assertion. Not only has the agent been identified, she boasts, but there is a new process to mass-produce the virus, which has made a blood test possible. “With the blood test,” she wraps up, “we can identify AIDS victims with essentially 100 percent certainty.”
Why were scientists certain in 1984 that HIV was the cause of AIDS? It was only three years after the outbreak of the mysterious disease. At the onset, no one knew where the illness originated, how it was transmitted, what caused it, or how many lives it would claim. Was Heckler’s assertion a substantial claim of fact or a hopeful shot in the dark, like Robert Gallo’s papers published a year earlier linking a different virus to AIDS?
Heckler steps off the podium as a tall man takes her place. It is Gallo, Chief of the National Cancer Institute’s Laboratory of Tumor Cell Biology. This year, Gallo is reserved, shrouded behind dark glasses. To the chagrin of the reporters, he speaks in highly technical language. His tone is already defensive. After a burst of critical questioning, the irate Gallo makes the most declarative statement he’s willing to give: “I think the agent is at hand that produces the disease.”
What made Gallo, a scientist with a troubled history of research, success marred with mistakes, decide to stand up once again and declare a discovery of major importance to the world? And why did the scientific community believe him? Today, the scientific consensus that HIV causes AIDS is bulletproof. But we may wonder where that consensus came from. What happened that makes us so sure today? Five months after the press conference, a reporter asked Gallo why the AIDS epidemic began. Gallo responded:
“No one can ever say with absolute certainty the origin of anything unless you’re there to document it and prove it at the time it arises. All you can do it assemble the facts that you can get your hands on after these events occur and draw the best estimate of what happened.”
Ghost at the Machine: Internet Addiction and Compulsive Computer Use
by Rachel VanCott
A rumble and rolling drum beat sound as the computer game starts up, followed by high tempo music. A moment later, the screen displays a swirling vortex behind an ancient stone doorway and a text field where I type in my account name and password. The key goes through and I click on the image of my character: a hulking steer-like biped, arrayed in green armor, wielding a hammer. When I started this game months ago, I affectionately named the burly cow “Thumper.”
In the game, my character charges down a dirt road and I begin to scan the digital savanna known as The Barrens. This is World of Warcraft (WoW)—an online game that brings players into a complex virtual world where they battle monsters or each other, completing quests and forming alliances. I no longer play, but I’ve come back to satisfy a nagging curiosity. There’s a chance that what I’m about to type might get me laughed out of The Barrens.
[Thumper]: …does anybody really think they’re addicted to World of Warcraft?
BarrensChat is a chat line for players. They can type into it to sound the alert when enemies attack, or seek help with difficult tasks. But most of the time, players just use BarrensChat to tell awful jokes and ridicule one another. So I don’t know what to expect.
For the first moment, nothing happens, and I think that my question will be ignored. Then responses start to trickle in:
- [Valanx]: I’ve known many people that are, Thumper.
- [Desecrate]: this game is easy to get addicted to
- [Valanx] whispers: I used to be addicted as well
- [Katojones]: you’re playing WoW and you’re researching addiction?????????
- [Desecrate]: I think that’s a sign of your own addiction
- [Valanx] whispers: used to play for 12-13 hours straight
- [Valanx] whispers: %^&*ed up my life once
- [Valanx] whispers: got kicked out of my house and my girl threatened to leave me
- [Valanx] whispers: …I know what it’s about.
His real name is Josh.
He doesn’t want to stop playing, but he wants to tell me more. So we talk over a voice communication system built into the game. Throughout our conversation, the sound of his voice is punctuated by the click of fingers on keyboard and the occasional sharp exhale and muttered curse as he continues to play.
Cosmos Incognito: Vera Rubin Shines Light on Dark Matter
Night after night, for hours at a time, Vera Rubin sat in the open air, her eye pressed to the telescope, her hand on the guider. She waited and watched. Occasionally, she nudged the controls of the instrument ever so slightly to keep the galaxy in the guiding crosshairs while it, millimeter by millimeter, traversed the evening sky. “I remember tracking Andromeda. Its center had this light, greenish glow. It always made me wonders if someone, an astronomer in our neighboring galaxy, was looking down on our own and watching us.”
Because the galaxy’s disk lies on an incline directed toward our planet, anything moving toward Earth….has its light shift into the blue part of the spectrum. The objects and regions receding from Earth, the ones rotating on the opposite side of the galaxy, emit light waves that get stretched out and hence appear redder to astronomers.
For six hours, Rubin tracked Andromeda’s gaseous knots, eager to capture a spectrum across the spiral’s width. When she finally finished her first exposure, the astronomer climbed down from the telescope’s cage, reached in and gently unfastened the photographic plate from its resting place in the spectrograph, and then slipped down to the observatory’s dark room. Inside, her hands began to tingle. Desperately, she tried not to let them shake as she treated the plate with the proper chemicals. Slowly, as if by magic, the lines of Andromeda’s spectrum materialized. It was like the uncovering of a secret message scribbled with invisible ink. Rubin’s trepidation turned to euphoria. At the sight of the banded lines, she knew she had the perfect procedure for measuring the motions of distant spirals.
Anxious to return to the telescope to collect even more spectra, Rubin left a visiting astronomer to finish cleaning the plate. Little did she know he was mistakenly washing away the photographic emulsion with hot water. Afterward, he was guilt-stricken, but to Rubin, losing the plate didn’t matter. She was too ecstatic that she and her colleague Kent Ford had finally found a way to probe the outer edges of far-off galaxies.
Exposure after exposure turned out as great as the first. Soon getting the spectra was second nature; interpreting them, however, was a bit puzzling. They were all so straight. Rubin was observing that Andromeda’s outermost stars raced around the spiral just as fast as the galaxy’s innermost stars. How, in the realm of physics, could this be? Brainstorming ideas, the astronomer began thinking in terms of what she could physically observe with a telescope. Perhaps some violent ejections of gas were stirring up the stars. Or, maybe, the gaseous knots had uncharacteristic orbits for some reason. “All my ideas turned out to be totally wrong,” she says, “but I didn’t know that then.”
Failing to explain the non-Newtonian observations did not prevent Rubin and Ford from writing up their findings; the results were published in the Astrophysical Journal in February 1970. Fellow astronomers still remained somewhat skeptical. Maybe it was just a fluke, a rotation only to be seen in Andromeda. Other galaxies, they charged, would certainly not exhibit this unexpected and unexplained behavior…