2004 Thesis Excerpts

Amitabh Avasthi Superfish: The Coming Blue Revolution

Katherine Bourzac Breaking Boundaries:Chimeras and Species

Jennifer Frazer Mold Fever: How a Bizarre Life Form Penetrated Popular Consciousness and Launched a Creeping Hysteria

Courtney Humphries Side Effects: The New Age of AIDS in America

Carolyn Johnson Neutrino Capital of the World

Megan Ogilvie Ocean Fertilization: Ecological Cure or Calamity

Mara Vatz Knowing When to Stop: The Investigation of Flight 191

Superfish: The Coming Blue Revolution
Amitabh Avasthi

Located on the eastern most tip of the North American landmass, St. John’s in Canada’s Newfoundland province boasts a link with the sea that is older than any other city on the continent. Over a thousand years ago, the Vikings were drawn to the region because of its incredible marine life. When Italian explorer—and fish trader—John Cabot landed there on St. John’s Day in 1497 the abundance of fish amazed him and his crew. Cabot returned to England with tales of a “new-found land” where fish could be hauled up in buckets. By 1620, the region was a major supplier of dried cod to countries as far away as Spain and Italy. France and England fought mightily to control this vast fishery business.

Four centuries later, St. John’s is now just another exotic travel getaway, a sleepy port town blessed with natural beauty, scenic drives, and historical monuments. But quiet rumblings are taking place there on the molecular level. Genetic tinkering in its laboratories is attracting the interest of the world’s fish consumers and industry alike. These fruits of biotechnology promise to match the discovery of fire itself. If the efforts succeed and ecological concerns are allayed, genetically modified fish—bred to grow at a phenomenal speed and resist disease—promise to revolutionize the aquaculture industry and restore St. John’s to its formal glory as the center of the global fish trade. But playing with fire has dangers as well. Some wonder if such attempts to remodel nature could have ecological consequences as disastrous and irreversible as a conflagration out of control.

Since the earliest days of animal domestication, humans have tried to improve the quality of their livestock through selective breeding. Though the results have been impressive, the process is generally slow and time-consuming, as it can usually take several generations of such selective breeding to achieve the desired traits in an animal. Breeding efforts are imprecise, and success is mostly a hit or miss affair.

In 1866, Austrian botanist and monk Gregor Mendel demonstrated how physical traits were transferred from parent to offspring through genes. Geneticists later came to realize that if they could somehow collect the genes responsible for specific traits and selectively add them to individual plants and animals, they could make designer plants and animals of their choice. But there was a problem. Science lacked the methods to extract, purify, and manipulate DNA, the molecule that genes are comprised of. Not until 1973 did Stanley Cohen of Stanford University and Herbert Boyer of the University of California, San Francisco, solve the problem by showing how DNA from one organism could be carefully snipped away at just the right point using enzymes as molecular scissors and be replaced with a gene from another organism. This method of gene splicing became the common means of transplanting genes from one species to another and led to the creation of the biotech industry. Scientists once had a dream, now they had the tools to realize it.

Breaking Boundaries:Chimeras and Species
Katherine Bourzac

Humans and mice are much more distantly related than goats and sheep, but chimeras between the two work surprisingly well. “It surprises me that it’s so viable,” graduate student Paul Davis said of the chimera model he uses to study disease pathways at Washington University in St. Louis. He and his advisor Samuel Stanley, a professor of medicine and microbiology at the university, repeatedly used words like “surprising” and unexpected” to describe their chimeras.

Goats and sheep are in different genera. Humans and mice are in the same kingdom (animals), phylum (back-boned animals), and class (mammals). We diverge before goats and sheep, at the order level – they scurry off with the other rodents, we with our big brains and opposable thumbs join the primates. But enough has been preserved throughout the course of evolution that tissues and cells from humans and mice can form chimeras.

Stanley’s lab implants human fetal tissues into adult mice to model human diseases. Davis explained how they create the chimeras. “We have collaboration with the birth defects center at Washington University and they send us fetal tissue at 90-92 days old. We take those fetal intestines and implant a small, centimeters-long tissue section into the back of the mouse. You slice the mouse open on the dorsal side [the back] and you implant the tissue and just close up the mouse.” The tissue grows “and you’ve got a human intestine” living in an easily accessible spot on the mouse’s back.

Stanley and Davis use a strain of mice, called severe combined immune deficient (SCID), bred for deficiencies in their immune system. SCID mice don’t have an important class of immune cells – those which, among other functions, cause transplant rejection. “We know we’re getting around tissue rejection because we’re using mice with no immune system, so they can’t really reject the [human] tissue.” These mice do not incorporate the human tissues to the extent that goat and sheep became integrated in Anderson’s overt chimeras. “You’re really using the mouse as a vessel to be the carrier for human tissue,” said Stanley.

Davis got involved with this work “because it was absolutely cool. The “first corollary” of microbiology, he said, “can be summed up like this: if you don’t have a model, you’re screwed. That’s the end-all, be-all….If there’s not a model in which to study your organism, don’t study it.” And SCID-human chimeras are “the best model you could ever have…for virtually any pathogen. Not only is it a model, it’s probably the best model you can get because it’s actual human tissue, not a mouse or ape but actual human tissue.”

“You can actually mimic a number of things that would be happening in the human in the mouse,” Stanley said. SCID-human chimeras have been used to model a number of processes in the human body. “To look at organogenesis – how an organ develops – it’s turned out to be a nice system. The other thing that’s been nice is the idea of studying human-specific pathogens,” agents of disease like bacteria. Scientists have used the chimeras to test early anti-HIV drugs and model diseases from cystic fibrosis to rheumatoid arthritis to cancer. Stanley and Davis study Entamoeba histolytica, an amoeba that causes dysentery (horrible diarrhea) and liver abscesses among other symptoms.

Davis said they hadn’t anticipated how well these SCID mouse-human chimeras would work. “It was kind of a grand experiment with no hypothesis – hey, let’s see if this would work.” They knew the SCID mice would not reject the tissue. “But I think it was to our surprise that it would accept the tissue….we were surprised that it wasn’t ignored by the mice,” Davis recounted. In other words, the mice go beyond not attacking the human tissue. When you make a new addition to your house that has a sink or a toilet, you add on to the plumbing. The mice do the same thing when the human tissue is added, growing new veins and arteries to provide a blood supply for the human intestine or liver or skin.

Read Katie’s entire thesis on MIT’s DSpace

Mold Fever: How a Bizarre Life Form Penetrated Popular Consciousness and Launched a Creeping Hysteria
Jennifer Frazer

Living creatures float in every breath we take. The air is a mist of life that coats every surface exposed to it with microorganisms. This is normal.

Among these organisms are the molds – fungi that specialize in decay. In recent years, these molds have also generated a furor – a storm of fears, litigation, rising insurance premiums, and a small industry specializing in detection and remediation. This is not normal. At least, it’s never happened before.

Humans have lived with molds for thousands of years in uneasy peace – especially compared with our tempestuous relationship with other microorganisms. Countless viruses and bacteria infect humans, but the number of major fungal infectious diseases can be counted on two hands. Ebola, plague, smallpox, tuberculosis, and other diseases caused by viruses and bacteria are the subjects of horrific legends and nightmares. Tinea, the fungal cause of athlete’s foot, is the subject of mildly amusing low-budget commercials.

But lately molds have been getting new attention. The illnesses some people have claimed are caused by mold are more nebulous, and in some ways, more frightening. Breathing difficulties, headaches, dizziness, flu-like symptoms, unexplained bleeding, hearing or memory loss, cancer…the list goes on and on. And it’s not just called mold anymore; it’s “toxic mold.”

Families come on the evening news to describe how mold has taken over their home – even their car! – making them perpetually sick. Moon-suited remediators are the only ones who enter such contaminated houses, as if they were “hot zones.”

Every fall, the news media describe how some public school has developed a mold problem and must be closed for clean-up.

Books and websites warn homeowners about the dangers of “toxic molds”, in particular, the black mold named Stachybotrys chartarum ( stack-ee-bot-ris kar-tar-um).

Insidious, silent, and deadly, this new threat has emerged, some claim, to threaten our lives. Others dismiss the concern as mass hysteria, brought out of nowhere by enterprising capitalists, and unsupported by scientific evidence.

“I’m just so fascinated by this phenomenon,” said Raymund King, the author of the 2003 book Toxic Mold Litigation. “It’s really a phenomenon. I practiced medicine for about 10 years before I became a lawyer, and I see it from two different perspectives.” His book, aimed at lawyers, published last July, and priced at $102.85, sold out in eight weeks.

Whatever the true cause, marriages, jobs, and health have all been damaged by close encounters with indoor mold. The insurance industry has also taken a financial beating, as mold claims have skyrocketed nationally. And those looking to exploit or profit on mold fever have caused needless headaches and confusion, sometimes ruining the cases of those with potentially legitimate mold claims.

Why are some people suddenly consumed with fear of “toxic mold?” Have the molds changed? Have our homes? Have we? Does mold truly cause horrific health problems, or is it just hype? The truth, according to a five-month investigation, lies somewhere in between.

Read Jennifer’s entire thesis on MIT’s DSpace

Side Effects: The New Age of AIDS in America
Courtney Humphries

When a new class of drugs called protease inhibitors emerged from the lab in 1996, everything changed for HIV-infected individuals in the U.S. The following year, studies found that a triple-drug combination reduced the levels of virus in the blood to the point where they were often undetectable. “All of a sudden [patients] just weren’t getting sick,” Heller said. “And the management of HIV, from the perspective of a doctor taking care of patients, it sort of—I don’t want to say became less challenging – but it became more rote.”

Heller’s patients have simply stopped dying. “I’m trying to think of the last time I saw somebody dying of AIDS,” he said, and paused for half-a-minute to think. “I guess it must have been five years ago, at least a patient of mine.” And five years ago such a statement would be unthinkable for a physician caring for HIV-infected patients.

Harvey Makadon, a primary care doctor at Beth Israel Deaconess Medical Center specializing in HIV/AIDS, also has not lost a patient to AIDS in four or five years. Not only are his patients living longer, the opportunistic infections that used to plague AIDS patients are now far more rare. “I haven’t seen a person with an opportunistic infection in probably three or four years,” said Makadon.

For those with access to care, these new medicines have changed the face of AIDS and they have done it far more dramatically than many people in the field would have thought possible. Vastly more people are living with HIV infection than are dying of AIDS. The Centers for Disease Control and Prevention (CDC) estimates that between 800,000 and 900,000 people are living with HIV infection in the U.S., and nearly 400,000 of those are living with AIDS. In 2002, 16,371 people died of AIDS.

Just as insulin treatment changed diabetes from a fatal disease to a chronic one, so HAART has changed the meaning of testing positive for HIV infection in the U.S. In the 1980s and early 1990s, finding out you were infected with HIV often meant dramatic life changes and coming to grips with impending mortality. Some quit jobs and abandoned long-term plans.

But some of these patients, resigned to certain death, received newer treatments and “suddenly it was, ‘Here is your life back. You’re not going to die,'” said Heller. “And a lot of these people who had put their careers on hold, and their lives on hold, and had not gone into relationships, and had sold their life insurance policies, and didn’t both building up their 401Ks” suddenly were given back their lives, but they had already abandoned the things they needed to have a life.

Psychologists dubbed this phenomenon the Lazarus Syndrome, because these patients, if not awakening from death, were returning to their lives after acclimating to the idea that death was at hand. But their new reality was far more complicated than simply waking up to restored health. The suddenly faced the complex financial and medical issues of someone living with a chronic disease. Many had gone on disability insurance during their illness, and now found themselves able and willing to work but afraid to lose their disability by looking for jobs.

From a medical standpoint, the man we call Bill Dudley is leading a life very similar to that of a patient taking medication for high blood pressure, and he represent the ideal in the medical treatment of HIV/AIDS. In the natural course of AIDS, symptoms of illness appear after a mean of eight to ten years. Dudley was fortunate in that he managed to stay healthy for many years until better medications came along.

In the early days of his infection, he was meticulous about his health, regularly working out and meditating. “Back then you were always prepared for the worst,” he said. Now he is less vigilant. “But I think part of that has to do with age. I never thought that I would actually see 50.”

Read Courtney’s entire thesis on MIT’s DSpace

Neutrino Capital of the World
Carolyn Johnson

Ray Davis’ work at Homestake uncovered what Scholberg called “the famous mystery of the disappearing solar neutrinos.” The solution to the mystery was far more complex than physicists anticipated, and Homestake played an important part in revealing the particle’s
true, rather wobbly identity. Scientists didn’t have to revamp their solar models or redesign their directors – they just had to reimagine neutrinos. In order for Scholberg’s “neutrino dance” explanation to hold true, the particle must have mass and travel slower than the speed of light. But those ideas didn’t hold with particle physics’ main theoretical platform, the so-called Standard Model. Perhaps the discrepancy between the old theory and the new result is most apparent in John Updike’s verse, which was written before neutrino oscillations were discovered:

Neutrinos, they are very small.

They have no charge; they have no mass;

they do not interact at all.

The earth is just a silly ball

To them, through which they pass

Like dustmaids down a drafty hall.

Neutrinos are indeed, small and chargeless. The poem’s popularity among physicists indicates they may be granted the poetic license to “pass like dustmaids down a drafty hall.” But things have changed since Updike wrote the poem. Neutrinos do have mass and they do interact.

Physicists are still arguing about what to do with the obsolescent Standard Model. What will fill the gap: string theory, grand unified theory, dustmaid theory? “Physicists,” Gilles observed, “aren’t anxious to change [theories] unless they’re positive.” In 2002 Davis shared the Nobel Prize for his discovery, which physicist Kevin Lesko called the “big shift, the paradigm shift in our understanding of the universe.” Ken Lande, who lived in Lead with his family for many summers while collaborating with Davis, often directs public attention to the important role that Homestake played in this drama as he canvasses for the scientific drama to continue in a new underground lab. “The…thing that happened here in South Dakota in the Homestake Mine, it started a brand new field: this is the field of neutrino astrophysics. So, it is worth remembering.”

Just as Davis was winning his Nobel Prize, the mine that had served as his laboratory was in its death throes. Mining is a destructive business, and companies spend years attempting to erase their footprint on the environment: cleaning the land, the water and the mine itself. Gilles’ house looks out over a deep canyon once filled with activity. There’s the number five winze airshaft, the area where the cutting-edge tube conveyor (brought all the way from Japan) used to run, the grain elevator-like Ross shaft where cages sped underground. “It was a tough duty when they were starting to tear [the mill buildings] down,” he said, describing the loss of a huge complex built into the hillside on the edge of town. “Everything you knew for a lifetime, they were tearing off the mountain. That was kind of discouraging.” Later, on our way to dinner we passed the bare hillside in the Murdy’s pickup truck. Gilles pointed out the ruined foundations where massive machines once stomped ore to a fine powder. Everyone sighed.

South Dakotans reluctant to abandon Homestake have put their support behind the particle they helped mine from obscurity. “Neutrino: A particle whose time has come” headlines that have peppered the local newspapers since the mine announced it was closing. The Rapid City Journal, which serves the western half of the state, has run 143 articles about neutrinos over the past three years even though it has no science section. In contrast, The New York Times has mentioned neutrinos in only 15 articles over the same time period. Charles Lamb, president of the South Dakota Academy of Science made the minute particles a priority in his inaugural speech among other important issues like cloning, biodiversity, climate change and space. The numerous, but hard to detect Lilliputians of the particle zoo have become the mascot for the proposed underground laboratory and for South Dakota’s future.

Read Carolyn’s entire thesis on MIT’s DSpace

Ocean Fertilization: Ecological Cure or Calamity
Megan Ogilvie

John Martin, an oceanographer from the Moss Landing Marine Laboratory, was one of the first scientists to detect that common species of phytoplankton and zooplankton contained trace metals, such as copper, zinc and iron in their chemical make-up. He realized that trace metals must be integral to phytoplankton growth if the microscopic organisms were using them at the molecular level. Martin developed new techniques for measuring metals in seawater that were clean and contaminant free. Armed with their new equipment techniques, Martin and his researchers went to work cataloging components of ocean water.

The results of the seawater testing shocked the oceanography community. Concentrations of trace metals known to be in ocean waters, such as iron, were detected at orders of magnitude lower than previously thought. And new trace metals, including zinc, cobalt and manganese, that had never before been documented, were found to be common in seawater.

During his trace metal experiments, Martin turned his attention to understanding the role phytoplankton play in regulating the global climate. He was intrigued by the barren ocean waters and set the task to try and figure out why these desolate zones were devoid of life. For lack of a better explanation, up to this point in time most scientists believed that zooplankton feeding on phytoplankton kept the plant-life low in these areas by voracious grazing, much like the way a field of cows eats a grass field bare. But Martin thought that there was something other than overeating zooplankton keeping parts of the ocean barren.

Martin developed a hypothesis that iron was a micronutrient needed for phytoplankton reproduction and growth, and the lack of this trace metal was the sole reason for the barren ocean waters. This became known as the iron hypothesis. Open ocean waters, like those of the Antarctic, equatorial Pacific, and Southern Oceans, Martin reasoned, were too far away from land masses to be naturally fertilized by dust storms blowing off the edge of continents that contained micronutrients, such as iron. According to Kenneth Coale, Martin “was the kind of guy who could put a bunch of seemingly disconnected information together…and whip it up into a theory that was all connected. [His iron hypothesis] was beautiful.”

To test his iron hypothesis Martin sent a team of researchers to the Antarctic Ocean to collect samples of phytoplankton-barren seawater. Iron was added to some seawater samples, while other samples, the controls, were left untreated. After several days under the same conditions, phytoplankton was thriving in the samples containing iron. The control samples were still barren. Further bottle experiments strengthened the hypothesis’s standing, and rocked both the oceanographic and the remainder of the scientific community. The iron hypothesis was, as Barber mentioned, a paradigm shift for oceanographers.

Martin then took his hypothesis even farther and suggested that the iron-ocean interactions may be partly responsible for past ice ages. During the ice ages, the climate was much drier than it is today. The atmosphere was a grimy swirl of dust swept up from vast stretches of deserts covering the land. If large amounts of this iron-rich dust were blown into areas of the ocean that lacked iron, the fertilized ocean would increase photosynthesis in plants, thereby sucking more carbon from the atmosphere into the ocean and cooling the planet.

Seeing the possibility of how close iron limitation may be linked to the global climate, Martin followed this conjecture with another, even more provocative speculation: dump enough iron into the ocean and you could reverse global warming. At a lecture at the Woods Hole Oceanographic Institute in 1988, Martin uttered what is undoubtedly his most famous quote: “Give me a tanker of iron, and I’ll give you an ice age.”

After publishing the results of his iron hypothesis bottle experiments and his ice age claims in the prominent British journal, Nature, Martin was courted by the press. His findings were published in many of the major science magazines, and the iron hypothesis – and the man behind it – soon surfaced in popular magazines and newspapers. Martin found himself on the talk-show circuit, discussing his iron hypothesis on Good Morning America, CNN, and the United Kingdom’s BBC.

Even though Martin’s bottle experiments strengthened his hypothesis, he faced doubts from other oceanographers, as it was yet to be shown that iron was the limiting nutrient to phytoplankton growth in the real world: the open ocean. Martin was challenged at every turn. According to colleagues, this contentious atmosphere was the kind he liked best.

To help resolve the controversy, Martin proposed to conduct ecosystem enrichments of the open ocean. But many scientists believed that experiments on whole ecosystems were risky, and it took several years to convince the National Science Foundation to endorse and fund an iron fertilization experiment.

Though Martin died of cancer shortly before the first iron fertilization experiment, dubbed Ironex I, his colleagues insisted that his research be continued. The first iron addition to the equatorial Pacific Ocean took place in the fall of 1993. Scientists involved with Ironex I fertilized a 64 square kilometer patch of ocean with iron. The results were astounding. The phytoplankton levels increased threefold. By all accounts, the ocean turned green.

Read Megan’s entire thesis on MIT’s DSpace

Knowing When to Stop: The Investigation of Flight 191
Mara Vatz

American Airlines Flight 191 began its long-haul trip to Los Angeles without trouble, although delays at O’Hare had put it a few minutes behind schedule. It was a mild spring day, 63 degrees with clear skies. At 3:02:38 Chicago time, the control tower cleared American Airlines flight 191 for takeoff on runway 32R heading northwest. A few seconds later, Captain Lux confirmed, “Ah—American one ninety-one underway.” That was the last communication Flight 191 had with the control tower.

As the plane accelerated down the runway, the cockpit voice recorder (CVR) picked up the voice of first officer James Dillard calling out the plane’s speed as it passed through eighty knots. Everything sounded normal until just two seconds before lift-off, when the CVR recorded a thump, followed by the word “damn” one second later—the last recorded sound in the cockpit. A controller in the tower watched as the plane lifted off. What he saw was almost beyond words. He shouted to the other controllers in the tower, “Look at this—look at this—blew up an engine. Equipment—we need equipment. He blew an engine. Holy ____.”

But the plane continued to gain altitude in what looked like a normal climb. The controller radioed to the captain, “American 191, you wanna come back and to what runway?” But there was no response. “He’s not talking to me,” the controller said. The plane began a shallow left turn. The turn got steeper and steeper—too steep. “He’s gonna lose a wing,” the controller said. “There he goes—there he goes.” The plane, only 580 feet and 20 seconds into the air, began to dive and plunged to the ground.

The plane crashed into an old out-of-service airport field that had long since been overshadowed by O’Hare. The space was being used as K-9 training grounds and extended right up to the edge of a trailer park, where mobile homes lined a few loops of pre-planned streets. Just on the other side of the park stood several oil storage tanks—an array of massive white cylinders with staircases winding around the outside that make the scale of the tanks look impossibly large. “If he’d a kept going, he’d a hit the oil tanks,” says Ken Miller, a man now in his fifties who has lived in the trailer park for over twenty-five years and today works in the park’s front office. “For miles around would’a been devastated if he’d a hit the oil tanks.”

Pieces of the shattered plane carved through some of the trailer homes and the fire on impact took the lives of two people on the ground. But the residents of the area still count themselves lucky. “He knew what he was doing,” says Miller. “Going down, he put it in the best place he could. We still credit that pilot.”

Miller was working in nearby Skokie at the time, and got a call from his boss who told him he’d better head home because there had been a plane crash. He says he could see the smoke from miles away. He rushed home to find that the streets were all blocked off. “There were nothing but fire trucks and hoses, everywhere,” he remembers. “The fuselage was out in the street over here,” he said, pointing through the window to the shady street that borders the old airfield.

The damage to the aircraft was extensive. “The air frame was, of course, severely broken up,” said investigator Henry C. Martinelli, a manager of aircraft systems engineering for American Airlines. Because the plane crashed with a full load of fuel, most of it was destroyed by the immense fire. The largest portions remaining were the engines, the landing gear and part of the tail. For weeks afterward, people sifted through the ashes, looking for parts and pieces of the airplane and for human remains. The whole area was under tight security, but even so, there were a few thefts. “There were some sick people,” Miller recalls. “One person parked on the toll way and walked over. He wanted to take something from one of the bodies, he wanted to take some lady’s ring. They caught some people trying to take pieces of the plane, but you know, they need every piece to put it all back together.”

The investigators didn’t have much to put back together; the damage to the plane was so complete. But they did have one major piece of the puzzle, a piece that hardly needed any putting together at all. Back on the runway, the left engine and pylon assembly (the structure that attaches the engine to the wing) was almost completely intact. And to many—though not to the NTSB—that was answer enough. Why did the plane crash? Because the engine fell off.

Of course, nothing is so simple. Like a child incessantly demanding to know “why?”, investigators are constantly searching for causes. In any investigation, answers along the way tend to open the door to more questions. The engine fell off, but why? Maybe it had pre-existing structural damage. If so, when, how, and why did the damage occur? It could have fallen off because of an explosion on board—terrorism or sabotage may have been involved. Again, who, when, why, and how?

Even these answers wouldn’t be enough. Understanding why the engine fell off was one thing, but figuring out why that caused the plane to crash was another. After all, DC-10s are designed to be flyable under catastrophic circumstances, even in the event of a complete engine loss. Why, then, couldn’t the pilots bring the plane back for an emergency landing? Maybe weather was a factor; or maybe the pilots were at fault. How experienced were they; were they well rested; what had they had to eat or drink the night before? All these questions and more needed to be addressed.

The investigation of Flight 191 very early on splintered into two clear but separate tracks. First, why did the engine fall off, and second, why did the loss of an engine cause the plane to crash? Behind every possible solution is at least one person—someone who caused, or more likely, failed to prevent a dangerous set of circumstances from arising. . . .[I]t can be almost impossible to distinguish between human and technological actions. Investigators could go back and forth forever and trace the line of causation back through time ad nauseum. As it turned out, perhaps the most difficult part of conducting the investigation was knowing when to stop.

Read Mara’s entire thesis on MIT’s DSpace