2013 Thesis Excerpts
Sign Here: Informed Consent in Personalized Medicine
The first human analyzed in the Personal Genome Project was born on August 28, 1954. At 58 years old, this Caucasian male weighs 246 pounds and measures in at 6 feet 5 inches. He is narcoleptic, dyslexic and has survived a heart attack and skin cancer. On any given day, he has a high level of fat in his O positive blood. Every night, he takes lovastatin, to lower his cholesterol levels. The man is a carrier for several possibly dangerous diseases, signaled by dormant “mistakes” in his genetic code that could result in lung disease in any future children.
The sum of his genes, known as his genome, is the recipe book to every protein his body creates. And now it has been sequenced, or read, letter by letter and analyzed for any currently known mutations, mistakes which can lead to deleterious health. This man’s entire genome, with all of its single nucleotide polymorphisms or unique single letters, is freely available for download to anyone with an Internet connection. It is a mere 272 megabytes and could fit comfortably on a compact disc.
Is his genome safe online? Can he be identified by his DNA? Did he know the risks before he donated his genome to science? The path to personalized medicine may prove not only to be a hurdle in science and technology, but also a challenge to scientific ethics.
George MacDonald Church is Profile One of the Personal Genome Project, his scientific quest to find the key to the human genome.
Hundreds of bottles of different chemicals line the seemingly endless shelves in his vast laboratory at Harvard Medical School. Dozens of post-doctoral, graduate and medical students bustle about; in this corner or that, an experiment of some sort is underway. Located just outside downtown Boston and surrounded by some of the world’s best hospitals, the modernist glass edifice buzzes with excitement about testing new ideas in genomic medicine.
Church has deep grey eyes, pale skin, a mane that won’t quit and a lumberjack beard that has long since given way to more grey. His full frame is shrouded with a Steve Jobs-style black top, with sleeves pulled up ready to work. He has a commanding baritone voice with a slight Southern charm, always speaking with a hint of marvel of the world. Church sits comfortably in his chair before a wall of manuals and books enhancing his already imposing stature. He is director of the National Institute of Health Center of Excellence in Genomic Science at Harvard, MIT & Washington University, and advisor to 22 biomedical companies, a handful of which he co-founded.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83832
Troubled Waters: The Battle Over Shipwrecks, Treasure and History at the Bottom of the Sea
Anything good down there? I asked David Hebb, nodding to the Hudson River slithering slowly outside his New York apartment window. Nothing of value, he said. And if there is anyone who knows, it’s Hebb.
David Hebb’s job is cooler than yours. He speaks six languages, travels all over the world, and you can barely find him on the internet. He has never advertised or sought out work in his current career and yet he has always been employed. No, he is not an international spy. Hebb is a historian, specializing in the treasure-heavy maritime history period from 1500 to 1800. Really, he’s an archival treasure hunter. He is the guy who finds wrecks for the people who find wrecks. “The strength that I think we bring to research,” Hebb said of himself and his colleagues, “is that we understand the general history, the administrative systems in place at the time which produce records, and where those records might be and how to use them.”
Here is how the process works: You say to Hebb, I’ve got some extra cash, and I want to find a sunken ship full of treasure in the Pacific. Hebb has a think on it and decides that focusing on the Manila Galleon trade is your best bet. Manila Galleons were Spanish ships that loaded silver and other goods in Acapulco, Mexico (then New Spain) and delivered them across the Pacific to Manila in the Philippines (then the Spanish East Indies) once a year.
Hebb’s first stop is the old British Museum Library where “that aroma from old and polished leather,” wafts through the large domed reading room and famous novelists inhabit the desks next to him. There he rummages through the records of every voyage of every Manila Galleon between 1568 and 1815. (Luckily, the Galleon records were condensed by two American scholars.) A promising wreck catches Hebb’s eye. ‘The largest vessel which had been constructed up to that time,” says one account of the wreck. Worth, ‘four and a half million pesos,” says another. He jets over to archives in Seville, Spain, where he knows there will be more information.
In the Archivo General de Indias—which occupies the original headquarters of the Spanish-Indies trade controlling body—Hebb digs through large legajos (bundles of documents) brought to him by porters and thinks, “god, I can’t read a word of this.” Slowly, he gets the hang of the strange handwriting and smudged ink. Eventually: Bingo. Buried in one legajo he finds records referring to the salvage of bronze cannon. The records tell him only the island nearest to where the ship went down, Saipan. But Hebb knows that Jesuit missionaries went to that island forty years after the ship sank and that they regularly communicated with their head porters back in Rome. Off to Rome goes Hebb. He spends days in the Jesuit Archives going through documents until he finds a clue: a letter in which a Jesuit missionary describes his visit to Agingan Point near where ‘the galleon had been wrecked in 1638.’ And that is how Hebb found the Nuestra Señora de la Concepción, perhaps one of the larger and richer galleons of her day.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83833
The streets of Roxbury, Massachusetts don’t look like a warzone. They aren’t littered with burnt shells and they don’t thunder with angry bootprints. But there is a standoff; There are two sides who have less than a geographical mile between them, but more than a century of ideology and distrust.
In the middle of January, the heart of Boston winter, I gathered with the underdog, a group of community protestors, at a local one-stop shop called Mr. G’s Plaza. With its bright blue awning and friendly white lettering, Mr. G’s is unmissable, just off one of the few cobblestone streets left in the neighborhood. I pulled into a nearby empty parking lot and the car shuddered off, chill already beginning to creep in the door cracks. Car horns and headlights whizzed by on Melnea Cass Avenue, interrupted occasionally by the shadow of a bus as it rumbled into the organized sprawl of Dudley Station. Just to the northwest loomed the Goliath adversary, Boston
University Medical Center, tall medical laboratories and gleaming clinics barely visible.
I was invited to Mr. G’s by community organizer and self-proclaimed “homeless mother, welfare advocate, homeless advocate,” Klare Allen. A woman of many trades, for the past decade, Allen has taken on the role of leader of a scrappy, fiercely committed, strikingly well-informed community group called Coalition Against The Bio-Lab.
The biolab in question is Boston University Medical Center’s National Emerging Infectious Diseases Laboratories, called the NEIDL (pronounced NEE-del), a research building erected in 2008. It’s one of two recently dedicated spaces in the United States for maximum containment or level 4 work – a rare designation necessary to work with highly regulated, often incurable diseases (e.g. the plague). Funded with $141 million from the National Institutes of Health and a little less than half that from the university, the elegantly swooped architecture of the blue building is tucked neatly in the eastern corner of the Medical Center campus. Protected by glass, gates, and guards, it’s irony incarnate: the building that ended a nation’s fear and began a community’s.
The fight, while seemingly over safety, illuminates a broader problem in U.S. biodefense tactics – a Jenga tower built on politicking, disorganization, and fears of terrorism. The biolab is one block of the tipping tower and pulling it out slowly – through lawsuits, historical precedents, modern-day protests – reveals a crumbling foundation of logic for how we got here in the first place and why Boston is now left with the effects.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83835
Take Two Notes and Call Me in the Morning: The Science of Music Therapy
The sun began setting around 4:30 p.m. on a cold day in February. At this time, roughly one third of people with dementia or moderate Alzheimer’s disease experience
sundowning—a period of time where their agitation and confusion about where they are and what they are doing will peak.
On the second floor of the Sherrill House Rehabilitation and Retirement Center in the Jamaica Plains neighborhood of Boston, thirty sundowning residents were seated in a loose ring following the perimeter of a well-lit room. A few were lying down in mobile hospital beds with heart-rate monitors hooked up and beeping quietly behind them. Some were seated in large leather wheelchairs. The majority seemed to be quite comfortable managing the straight-backed armless chairs that clearly accompanied the five square tables used for small meals and other activities. Aside from the attending nurses, not a single person had a strand of color left on her head.
The room was wallpapered in cream and forest green, and the late afternoon sunlight lent a warm glow to gold trims and accents. Despite the lazy catnap setting, the atmosphere was anxious. A low mumble filled the air, from residents addressing ghosts or the tops of their own feet. Some residents, mentally conditioned for decades to leave work or attend to afterschool activities, were clearly restless—their eyes darted back and forth, their hands tapped the glass tabletops, they rocked back and forth and to and fro. Two stood up to walk. The nurses called the standing residents by name (“Catherine! Where are you going?” “Arthur, come sit back down.”) and tried to get them settled in. After all, the music was coming.
And here they came—two young women with guitars slung over their shoulders. Their names were Lauren and Shir, both students in music therapy at the Berklee College of Music and interns under Dianne Tow, the only full-time music therapist at Sherrill House. They strolled into the atrium with big smiles on their faces.
The first song was “My Bonnie Lies Over the Ocean.” As a mumbled, almost unconsciously uttered chorus joined Lauren’s strong clear voice, Shir walked around passing out plastic eggs filled with beads, a simple rhythm instrument that the residents could bounce to keep the beat. A gentle murmur of “Mmhmm, mmhmm” and grunts of approval punctuated the end of the song.
Their set was composed of songs like “Que Sara Sara,” Elvis Presley’s “All Shook Up” and “Hound Dog,” “That’s Amore,” and Motown classics “My Girl” and “My Guy.” The musicians switched the role of lead singer every two songs, never halting the stream of music except to ask the residents questions and coax out some participation. As the musicians strummed their guitars and sang, they walked around and made eye contact with each and every resident all around the room.
During the 45 minutes that the girls played, many residents were captivated with the music (or dead asleep with mouths wide open), keeping beat with the shakers and vocalizing the melody or words to the song. But resident Catherine was restless. She stood up multiple times, making a break for the door because she had to go, she had to leave, she had to pick the kids up from school. Shir and the nurse got her to sit back down, but it wasn’t until Lauren began singing Smokey Robinson’s “Tracks of My Tears” that Catherine went still.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83836
Living in the Shadow of Mauna Loa
The largest volcano on Earth is taking a nap. After twenty-nine years and counting, no one is quite sure when Hawaii’s Mauna Loa volcano will again wake up. But odds are that it will be within our lifetime—sometime in the next couple of years or decades—and it will be spectacular.
Stretches of hot red lava will fountain up violently, hundreds of feet into the air, like a row of glowing geysers. An underground molten ocean will unleash, where waves of lava pour out of fresh giant cracks. A plume of sulfuric-rich smoke will climb into the sky, like a huge smoke stack. Emanating from the cracks, flows, and fountains, heat will flush cheeks from a dozen feet away. A volcanic chorus of splattering, hissing, crackling, and oozing noises will thunder in the ears.
It paints a hellish scene, but does it really pose a danger? It all depends on whether lava is confined to the mountain’s highest levels, where even trees are not invited—or, as scientists and emergency managers fear, migrates downslope to the realm of people and commerce.
And it is not an unfounded fear. History warns us that Mauna Loa’s current silence is anomalous. Etched into the rocky mountainside is a story of repetition: Over and over lava flows have painted the land red. Mauna Loa has erupted thirty-three times since 1843, when people started recording such events, an average of once every five years. And over the past 3,000 years, the geologic record testifies that the volcano has erupted an average of every six years. That means even if the next Mauna Loa eruption spares the Big Island community, the second, third, or fourth eruptions will likely not be so kind. It is just a matter of time.
Adding to the threat, Mauna Loa eruptions can occur along different points of the mountain. While most eruptions start at the mountain’s very top, the eruption source, the physical point where lava comes spewing out of the ground, can move. Around forty-five percent of historical eruption sites have shifted to lower elevations—generally to the northeastern or southwestern sides of the mountain. Not a trivial amount.
Lying at the foot of the northeastern side like a welcome mat is the island’s largest city, Hilo. Despite being the most recently threatened population by Mauna Loa back in 1984, Hilo residents are largely apathetic to their risk, said Frank Trusdell, a scientist at the Hawaiian Volcano Observatory and the world’s leading Mauna Loa geologist. Part of the issue is the city’s growing population, which has ballooned by nearly a third since the last eruption, from about 35,200 to 43,200. In response, development has pushed farther up Mauna Loa’s slopes.
It has been over twice as long since Mauna Loa flows terrorized the southwestern side. Since that last eruption in 1950, subdivisions have sprung up like dandelions, including the world’s largest, Hawaiian Ocean View Estates. And in over sixty years, the number of residents on the entire southwestern side has climbed from 8,000 to over 18,400. Tourism in the Big Island, especially on the western coast, has also skyrocketed in recent decades. Many newcomers and visitors are not even aware that Mauna Loa is still active, said Trusdell.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83837
Grey Harvest: Wolf Hunting in America’s Heartland
The wolf dens were just ahead, tucked into the ridge above the frozen marsh. It was early November 2012, and winter in northern Minnesota had already arrived. Light snow swirled amidst old-growth cedars as a tall, barrel-chested environmentalist named
Barry Babcock split off from the trail, his boots crunching on frost and fallen birch. As we trudged along, I asked Babcock about the chances of seeing a grey wolf patrolling near its home. He didn’t reply at first. He just stopped and squinted up through the lattice of branches, listening to the calls of the circling birds.
“I can usually tell by the ravens,” he said. “Ravens follow the wolves.”
Babcock’s laconic baritone was hushed, almost conspiratorial. He knew we weren’t the only ones looking for wolves in these woods, just as he knew that, unlike us, these others would be carrying rifles instead of corncob pipes.
After about thirty minutes, we reached the first den. It was a small hole three feet deep and about a foot in diameter, likely dug by a pregnant female wolf to breed her pups over winter. Babcock crouched down to inspect it. Something darted in the dark. A roly-poly porcupine had taken up occupancy. Whatever wolves once lived here, they had either moved on or been killed.
“They say there are so many wolves out here, well, where are they?” Babcock said, a strain of anger hovering just below the surface of his even-keeled voice. He stood up slowly, shook his head, and stared out over the pond. “How many dead wolves do they need?”
For the first time in state history, Minnesota was hunting wolves. For much of the past century, the state’s three million acres of dense forest had been home to the last native grey wolves in the continental United States. Then, last January, on the heels of the federal government’s decision to remove the wolf from the Endangered Species List, Minnesota immediately authorized a recreational “harvest.” The scale of the cull was unprecedented: Of the roughly 3,000 wolves estimated to roam the state, over 400 would be shot and killed by year’s end.
Minnesota game management officials maintained that the carefully orchestrated hunt would bring the wolf population back down to sustainable and practical levels. Livestock farmers in the northern regions of the state weren’t about to complain; wolves, they claimed, had threatened their livelihood for years. Recreational hunters, many of whom blame the resurgent predator for a depleted white-tailed deer population, eagerly awaited the opportunity to stalk a species that had been off limits for nearly forty years.
The hunt was not without ecological risk. Like bald eagles, great white sharks, and other apex predators at the top of the food chain, wolves stabilize forest ecosystems by regulating the populations of their prey. They keep deer and elk herds in check, thus ensuring that the herbivores don’t overgraze on young timber, which in turn robs songbirds of their nesting habitats, beavers of their dam building materials, and so on. If Minnesota were to lose all of its wolves, evidence suggests that the state’s woodlands would teeter on the brink of biological chaos.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83838
Champagne for the Blind: The Story of Paul Bach-y-Rita, Neuroscience’s Forgotten Genius
Last January, I flew out to the heartland and drove up to Bach-y-Rita’s old home in a rented Ford Fiesta. He lived in a small house set back from the street, atop a hill just outside downtown Madison. Still residing there is Bach-y-Rita’s short and dark-haired widow, Esther, as well as his youngest daughter, Andrea, Andrea’s boyfriend, three cats, and one tiny, trembling, gray poodle. …
At night, I slept in the former bedroom of one of Bach-y-Rita’s four daughters. Each morning, I hunkered down in the sun-lit den. The house has an open floor plan, with big archways instead of doors, and from my seat I could see Esther bustling about in search of her husband’s papers. She brought over newspaper clippings, scientific articles, Betamax tapes, books in French and Spanish, photocopies upon photocopies of the same old letter. There were three flash drives crammed full of files and huge photo albums with padded white covers. Esther and I spent one afternoon resurrecting an 80s microcassette player, coaxing it to play back a tinny version of Bach-y-Rita’s voice.
Prized among the findings is a green hanging folder, full of typed essays numbered in Esther’s hand. These are the unfinished chapters from Bach-y-Rita’s unpublished memoirs, a side project he worked on in the last few years before his death. I am the first person outside of the Bach-y-Rita family to read this stack of pages. They are the closest thing to a conversation he and I will ever have.
“I always meant to do something with those,” Esther tells me. “But it was too painful.”
There are almost three dozen chapters in all, in various states of polish, running anywhere from ten pages to three sentences long. They range from nostalgic stories about Bach-y-Rita’s childhood to serious treatises on technical subjects. … Clipped to the back of one chapter about youth baseball is a pitch letter to Woody Allen, encouraging the director to use the piece as inspiration for a new movie. (Allen never wrote back.)
Bach-y-Rita appears to have wrestled most with the memoir’s opening chapter. There are four different drafts, each substantially different. He first likens the brain to a computer, then changes it to a monarch butterfly, then to a vast landscape of rivers and forests. He tries to summarize his life in a few grand strokes.
“This is the story of a 40 year personal search for the brain’s treasures,” he wrote in one version. “Like all sagas, this long journey is full of twists and turns, successes and failures, alliances formed and broken, friendships and bitter rivalries, support and sabotage. There is no science without scientists and the people around them, and the influence of the world and times in which they live their very human lives.”
These beginning drafts are one of the only places where I can sense any doubt in Bach-y-Rita. He is attempting to make sense of the patterns in his life, to find lessons in the places where he did or did not triumph.
My favorite of all his opening lines were one of the last he wrote, just a few months after his cancer diagnosis in 2004.
“This is an adventure story.”
Out of Africa and Into the Sunshine State: Tracking an Exotic Invader
Todd Campbell was driving southbound on I-75 when he got the call that changed his life. The year was 2002, and a friend and fellow biologist called to talk reptiles. Campbell mentioned he was en route to Miami, about to cross the bridge from Cape Coral into Fort Myers.
“You gotta go see the monitors,” his friend said.
“What the hell are you talking about?” Campbell recalls asking.
“Go to Cape Coral, trust me,” his friend promised. He suggested Campbell head to the very southwest tip of Cape Coral and cruise the streets, talk to local residents. See what he could stir up. An invasion was unfolding that few outsiders knew about: Nile monitors, enormous carnivorous lizards, had become established and were breeding in the city—potentially a lot, Campbell’s friend believed.
Beside himself with excitement, Campbell took the advice and made a beeline for Cape Coral. The pony-tailed, suntanned herpetologist was in the middle of a post-doc position at the University of Tennessee, working in the lab of one of the world’s foremost experts on invasive species. His research on a small lizard called the Cuban brown anole brought him to south Florida, where the animal had been displacing the region’s native anole species for decades. Despite the glut in subjects to study, he’d had several false starts and was now unsure of the direction his work would take. Rumor of a giant lizard run amok was a godsend.
Cape Coral lies on Florida’s Gulf coast, about two-thirds down the state’s length, on a thick peninsula ringed by barrier islands. A little to the north lie the white sand beaches of Sarasota; a couple hours to the south lie the iconic green vistas of the Everglades. Few unpaved places remain in Cape Coral, but you can still catch a glimpse of the remnant pine flatwoods and mangrove-thick wetlands that formerly covered the area. You might imagine exotic lizards would be attracted to these tropical refuges, but instead, Campbell headed for the city’s matrix of canals and neighborhoods. Unlike Floridian icons like the manatee, leatherback sea turtle, and panther, which are highly sensitive to development, the Nile monitor thrives in close proximity to humans. Campbell’s visit didn’t take long to pay off. Within five minutes of driving around the southwest corner, he spotted a pair of older men power walking down the street. He asked if they’d seen any big lizards around the area.
“Yeah,” one of them answered. “I watched one shred a bunny in my backyard two weeks ago.”
Nile monitors, smaller cousins to the famed Komodo dragon, grow into six feet of carnivorous, ill-tempered muscle. Their size and aggression make them poor candidates for the exotic animal trade, but cheap, diminutive juvenile Niles nevertheless obtained popularity as pets in the 1990s. Now the descendants of released and escaped pet monitors were growing fat on a buffet of Florida’s native wildlife—and spreading.
On July 23, 2006, Ed Newcomer, an undercover Fish and Wildlife agent, finally managed to catch Hisayoshi Kojima. After his plane descended into Los Angeles, Kojima had hidden his valuable cargo in a slim wooden box and attempted to exit the airport. But a suspicious customs official detained him and notified the agent. When Kojima first saw Newcomer, he seemed relieved, thinking him a friend. Instead, Newcomer showed Kojima his badge and arrested him for smuggling.
This was a triumphant moment for Newcomer. He had been trying to catch Kojima in the act since 2003, having infiltrated his smuggling ring. The Fish and Wildlife service had been after Kojima even longer than that, with Kojima’s name first being tied to an infamous case back in 1995. Other agents had attempted to unearth enough evidence to arrest the smuggler, but without success.
Kojima earned his livelihood from illicit activities, smuggling and then selling his contraband for tens of thousands of dollars. It was remarkably easy for him to sneak his illegal goods of choice across country borders.
Kojima considered himself the Indiana Jones of smuggling. With his round, friendly, almost-boyish face, he hardly seemed the criminal type. He didn’t deal in weapons, drugs or explosives, but something more unusual; he made his fortune selling rare, poached butterflies. When Newcomer first visited Koiima’s small apartment in Los Angeles, he saw shelves stuffed with rare insects, both dead and alive, all ready to sell to anyone willing to pay the price. Customers loved him because his specimens were of the highest quality and his prices were the lowest. Of course, competing salesmen hated him for the same reasons.
Even so, by the end of the undercover sting, Newcomer had spent $14,500 on various purchases, including two Queen Alexandria specimens that Kojima sold to him for $8,500.
Human’s love affair with butterflies spans thousands of years. Throughout history, they have ben included in mythology, depicted in art, and written about in literature. Paintings of butterflies go as far back as 1350 B.C. in Thebes, Egypt, and the Greek word for butterfly, psyche, is the same word that is used for the human soul. Scientists have gradually unraveled some of the secrets of caterpillars’ miraculous metamorphosis into butterflies and engineers continue to study the nanostructures of their iridescent wing scales in the hopes of creating new pigments.
Ecologists have learned that some butterflies’ spectacular wings are brightly colored to indicate that they are poisonous or unpalatable, while other innocuous species mimic the appearance of poisonous ones. Some have brilliant eyespots that spook animals into believing that the butterfly is much larger than it is. It is ironic that the butterfly’s beauty, which originally evolved to ward off predators, has attracted the attention of the most formidable predator of all: mankind.
Full thesis here: http://dspace.mit.edu/handle/1721.1/83840