2006 Thesis Excerpts

Emily Anthes The Chosen Genes: Jews, Genetics, and the Future of Ethnic Medicine

Selby Cull From Gondwanaland with Love: The Geologic Adventures of the City of Boston

Phil McKenna Winging It: A Bold Step Toward the Whooping Crane’s Return

Susan Nasr The Buffalo Wars

Stephen Ornes ‘If it Quacks Like a Sphere’ — the Million Dollar Problem

Michelle Sipics Abandoned Minds: The Escalating Crisis of Geriatric Mental Illness

The Chosen Genes: Jews, Genetics, and the Future of Ethnic Medicine
Emily Anthes

It’s an achingly cold December night — unseasonably so, the city’s natives insist — and young Jewish couples from all over Chicago are pulling into the parking lot at Emmanuel Congregation, a Reform synagogue set just yards form the freezing waters of Lake Michigan.

Their breath visible in the night air, they file into the brick building, into a colorful social hall adjacent to the sanctuary where services are held each Friday and Saturday. They head for a long banquet table, help themselves to food from a kosher buffet: fruit salad, deli sandwiches (a variety of meats, but, of course, no cheese), chocolate chip cookies. They settle around seven round tables. Conversation revolves around dating and marriage, what it’s like to be young and Jewish in Chicago. Husbands get second helpings of cookies. Wives drop not-so-subtle hints about what they want for Hannukah.

And then everyone goes silent. At the front of the room, a young woman with curly brown hair launches into a presentation on the basics of human molecular genetics. From her place beside a large projection screen, Dania D’Achille explains that DNA, the genetic information contained in each cell of the human body, is merely a set of instructions the body uses to assemble proteins. With diagrams and drawings, D’Achille earnestly describes how we inherit these instructions from our parents, and what can go wrong if the body makes a mistake.

"You can have harmful gene changes that can lead to disease," says D’Achille, who spends her days working as a genetics counselor at Chicago’s Children’s Memorial Hospital. "By changing the structure of the gene in some way, that’s going to change the structure of the protein." And that can cause diseases, disabilities, or birth defects.

After breezing though these basics with the nonchalance of someone who’s done it many times before, D’Achille pauses and faces the room, asking the obvious question: "So," she says, "why are we here?"

After dinner, everyone will complete family histories and medical consent forms. Table by table, they will file into a room across the hall. They will roll up their sleeves and proffer their veins to lab technicians. They will switch naturally from asking how much blood will be drawn ("About two tablespoons") to asking whether the cookies offered afterward will be kosher ("Of course.") And, as the Chicago Center for Jewish Genetic Disorders wraps up its screening, the participants will be sent off with a tuft of gauze, a bandage, and a promise to hear in two to four weeks about the genetic destiny of their future children.

Though Jewish communities exist worldwide, many of today’s Jews — who are largely descended from a small, insular founding population — exhibit remarkable genetic similarities. Historical events that wiped out large swaths of the world’s Jews, coupled with cultural norms that largely discouraged the survivors from marrying outside the often isolated community, have helped create a gene pool with less variation than that of the general public. The result has been a shift in the frequency of certain genetic mutations, with some becoming more common and others becoming less so. These mutations include those that cause disease, which means that certain diseases are concentrated among Ashkenazi Jews — there are at least 18 diseases or disease variants prevalent predominantly among this group — while others are rare or nonexistent.

Each human being has certain genes that cause or predispose him to disease. In the ideal medical future, scientists will have hyperfast gene analyzers able to sequence anyone’s DNA in a matter of minutes. In that future, a patient could have his entire sequence of DNA screened for mutations that cause or predispose him to disease, and health care would be truly individualized to fit the genetic profile of each patient. But science isn’t yet able to make this future a reality; DNA sequencing remains too time-consuming and expensive to allow for such completely individualized medicine. In the meantime, scientists have discovered a useful shortcut: race and ethnicity.

Scientists are discovering that many genes vary across racial and ethnic lines. Every population of humans that has been reproductively isolated for some period of time — and that means all humans — has developed its own genetic characteristics. People who have the same geographic ancestry are more likely, on average, to be genetically similar than people who do not. That means that doctors can use a patient’s race or ethnicity — both of which are indicators of ancestry — to make inferences about his genes, including his likelihood of developing certain diseases. The result, in recent years, has been a decided push toward race-and ethnicity-based medicine, in which doctors and scientists use racial and ethnic groups not only to study disease, but also to treat it.

It’s an approach that contains an enormous amount of both promise and peril — in differing proportions, depending on whom you ask. Examining the genetics of races or ethnicities presents an incredible shortcut for scientists trying to prevent, treat, and cure disease. But such research also sparks fears of discrimination and has prompted critics to pose many troubling "what-ifs?" What if genetic research on ethnic groups reinforces social stereotypes? What if genetic knowledge about differences in disease predisposition creates medical racial profiling, leading to insurance and workplace discrimination and widening health care disparities? And what if, in the face of all these concerns, it’s not even good medicine?

But in at least one population, the hypotheticals can begin to be answered. For the past half-century, Jewish communities — because of their unique genetic heritage and their willingness to volunteer for study — have been getting the kind of genetic scrutiny that many other populations can expect in the near future. Those decades of experience with Jewish communities suggest that, as scientists improve their ability to characterize and analyze the differences between human populations, medical breakthroughs will perpetually be pitted against social ramifications.

"And that’s the big ethical question in general: do we want to know something?" said Bob Pollack, the director of the Center for the Study of Science and Religion at Columbia University. "Can genetic information be toxic?"

Jews, Pollack said, are the canaries in the cave. If you want to know if the air is toxic, he said, look at genetics and Jewish communities.

Read Emily’s entire thesis on MIT’s DSpace

From Gondwanaland with Love: The Geologic Adventures of the City of Boston
Selby Cull

Trilobites weren’t the only problem. One year after Rogers visited Hayward’s Quarry, Thomas Henry Huxley described a new Triassic reptile from South Africa, later named Lystrosaurus, literally "the shovel reptile." Aptly named (its head looked like a shovel), the plant-eating reptile was about the size of a large pig. It lived around 220 million years ago, at the beginning of the age of dinosaurs.

Like trilobites, Lystrosaurs were turning up everywhere: in South America, in China, in India, Antarctica, and Russia. Here was an animal that could not swim, float, or fly from one continent to another. How did it come to live on so many different continents?

The situation only became more confusing. Glossopteris , the fern-like tree that had dominated continents around 200 million years ago, turned up in rocks in India in 1828 – then in Southern Africa, then Brazil, the Falkland Islands, the Argentine Republic, Australia, New Guinea, and, to the extreme consternation of geologists, Antarctica. That’s a lot of oceans to cross, especially for a small tree.

Cynognathus , a land reptile, and Mesosaurus , a freshwater swimming reptile, followed the same pattern. The southern continents, which differ so obviously in their flora and fauna today, seemed to have shared nothing but the same flora and fauna from about 300 to 200 million years ago.

Darwin and Wallace had shifted biologists’ views on the origin of species. Now their ideas forced geologists to change the way they thought. What could explain the strange distribution of trilobites, shovel reptiles, ancient ferns, and myriad other fossils?

Animals and plants could evolve, change their forms, migrate – but surely continents could not. Instead, thought early geologists, they must once have been connected by bridges of land.

In 1885, the Austrian geologist Edouard Suess proposed that land bridges had once linked South America, India, Australia, Africa, and Antarctica. The continents, thus joined, would form a "supercontinent," which Suess named "Gondwanaland," after the Gondwana province of India were Glossopteris was first found.

Land bridges, Suess argued, had formed as a result of the cooling of the Earth. Suess and most other geologists of the day believed that the early Earth had been molten, and that, as it cooled, the surface shrank. Mountain ranges formed where it buckled, like the crinkles on the surface of a balloon whose air is escaping. Erosion could then grind them down, and the land bridges would sink out of sight below the ocean.

Land bridges seemed to answer all the fossil distribution problems. Geologists could construct land bridges to explain all sorts of strange distribution patterns, including parallels between living animals on separate continents. Since they needed no geological evidence to propose a "sunken" land bridge, they could build one just about anywhere.

Soon enterprising geologists had woven the entire globe with strings of land bridges. Insectivores migrated between Haiti and western Africa via an Atlantic connection, which was cut diagonally by a bridge that allowed rodents to go from Brazil to northwest Africa. Raccoons and bears made the jump from South America to Asia via a special Pacific Ocean bridge. Two Atlantic bridges allowed the Anchitherium horse to go from Spain to the United States, and mastodons to travel between Africa and Florida. Aardvarks migrated from Mexico to Ethiopia, armadillos from Latin America to southern France, and saber-tooth tigers from Russia to Canada . Somehow, freshwater mussels migrated across a bridge between South America and Africa .

As the century turned, Boston’s trilobites added another tangle to the web. Geologists pointed out that Boston’s trilobites were the same as those found in southeastern Newfoundland, Wales, southern England, and eastern Scandinavia – but vastly different from those found in New York, northwestern Newfoundland, northern England, and western Scandinavia. The Boston-type trilobites sat on slivers of land bordering the Atlantic on either side, sandwiched between realms of very different trilobites.

It wasn’t just trilobites. The sliver of land that held Boston and southeastern Newfoundland had completely different species of brachipodos, gastropods, hyoliths, and conchostracoids than the rest of North America. It almost seemed as if Boston didn’t belong to North America at all. In Europe, geologists noticed the same thing: Southern England’s trilobites didn’t match those of northern England – they matched Boston. Western Scandinavia did not match eastern Scandinavia – it matched Boston. It was almost as if northern England and western Scandinavia didn’t belong to Europe at all.

What on Earth had gone on here? Naturalists, locked into the idea that continents were fixed and unchanging, scratched their heads and drew ever more complex systems of land bridges, spacing them with barriers like mountains that would prevent some species from ending up in the wrong places. It was, without a doubt, a big, rocky mess.

Read Selby’s entire thesis on MIT’s DSpace

Winging It: A Bold Step Toward the Whooping Crane’s Return
Phil McKenna

Wildlife biologist Richard Urbanek had been watching the sandhills all morning from a nearby truck. As soon as he saw the whoopers join them he pulled up next to intern biologist Stacie Castelda and lowered his window excitedly. “They’re with the sandhills, the sandhills are migrating, don’t let them out of your sight!" he yelled, before speeding after the departing birds.

Castelda and a co-worker, each in separate vehicles, tore down the gravel road in hot pursuit of Urbanek and the quickly departing birds. With winds out of the northwest approaching forty miles per hour, it was nearly impossible for biologists on the ground to keep up, but they had to try. At some point in the day, perhaps minutes or hours later, the birds would attempt to land. If they picked a bad spot, like a crowded public park or the fenced-in yard of a high security prison—both of which had been attempted by young cranes in the past—the biologists needed to be there to quickly move the birds to a safer location.

Since late October, a group of pilots had been on call seven days a week. With an hour’s notice they could be airborne and supporting the tracking effort from one of two small airplanes. But on Thanksgiving Day, the pilots were off. The ground crew was on its own. The replacement cost per bird was estimated at $160,000. The human investment the biologists placed in hatching, rearing, and personally nurturing each bird prior to migration was incalculable. Losing even one of the four was not something they wanted to consider.

For weeks, Castelda had been ready to follow the whoopers whenever they departed. She kept a backpack in her work vehicle with a sleeping bag and enough clothes to last several weeks. Detailed atlases of every state between Wisconsin and Florida were stacked in a crate behind her seat. To keep an eye on the birds, she carried a pair of binoculars, a spotting scope, a hand-held radio antenna, and a laptop computer to download satellite tracking information. A larger antenna, the size of an old home TV antenna, was mounted to her vehicle’s rooftop.

Each whooping crane had a lightweight radio transmitter affixed to a leg. In that way, biologists could detect an individual bird’s signals up to thirty miles away from the ground or as far as a hundred miles away from an airplane. Three of the four direct release birds also carried small satellite transmitters. These devices gave precise locations for the birds—sometimes within a few meters—every few days.

Moreover, Castelda carried a large white crane suit that would provide enough of a disguise to allow her to approach and capture any of the young fledglings that might lose their way or get into trouble.

Taking separate routes, the three biologists triangulated the birds’ positions as they sped down southern Wisconsin’s highways. They tracked the birds southeast from Necedah before hitting heavy traffic near the Wisconsin-Illinois border just north of Chicago. Tied up by tollbooths, the biologists soon lost the young whoopers’ signals. The birds most likely continued on ahead out of the biologists’ range, but they could also have landed in a low-lying area where their signal couldn’t be detected. Unsure of the birds’ location, they fanned out and continued searching through Illinois and across northern Indiana. By nightfall, they were still unable to locate the birds and went to bed hoping the satellite transmitters would soon reveal their locations.

Read Phil’s entire thesis on MIT’s DSpace

The Buffalo Wars
Susan Nasr

Accompanying the problem of buffalo expansion has been that of disease. Yellowstone managers first detected brucellosis in 1917, after noticing stillbirths at the Buffalo Ranch . No one knows when the buffalo became infected, though historians believe it happened some time after the turn of the century. To Brucella abortus , buffalo have always been an ideal target, an enormous mass of flesh to colonize. But the bacteria could not have planned their entry into buffalo. Something must have carried them there.

Cattle living inside the park were the likely source, and several possibilities for transmission have been considered. In 1904, a scout on a government mission plucked a female buffalo calf from Yellowstone ‘s wild herd, nursed her on a milk cow, and deposited her at the Buffalo Ranch. If that cow was infected, the slurping calf might have swallowed live bacteria, but historian and biologist Mary Meagher finds this unlikely. There are other cows, however, that could have been the transmitters. For many years, hotels and outposts throughout the park kept cattle on premises in order to feed guests. An infected cow could have dropped a stillborn fetus while grazing, and a buffalo out to pasture could have licked it and gotten the disease. Meagher thinks this happened around 1915, when buffalo from the Ranch were pastured near some grazing cattle.

Regardless of the cow responsible, Yellowstone at first did little to manage the disease. They focused on feeding and culling buffalo to keep them in the park….By the 1940s, the park established a brucellosis testing facility. Park Service rangers tried a questionable buffalo vaccine and continued winter feeding but did little else. They thought it impossible eradicate the disease, and even unwise to do so, as a “clean” herd might suffer a massive outbreak later.

The Park ran trials in the 1960s, testing, slaughtering, and vaccinating small groups of buffalo, but concluded that the “never-ending” process would leave few buffalo for visitors to see. They instituted a new strategy of chasing and shooting wanderers at park borders.

Throughout the 1970s, the livestock industry came after Yellowstone like a stampede, calling on the Park to rid its buffalo of brucellosis. The Livestock Conservation Association, U.S. Animal Health Association, Wyoming Livestock and Sanitary Board, Wyoming Stockgrowers Association, and Montana Board of Livestock all made public statements asking the Park Service to reinstate testing, vaccination, and slaughter to eradicate the disease. The Park Service deflected them with polite letters, continuing its single solution—chasing and gunning down those that breached the park’s borders.

In the late 1970s, the Park relaxed even further. On Department of Interior orders, rangers stopped killing buffalo that stepped over park lines, leaving states to deal with the wanderers. Montana issued hunting licenses. The hunts drew so many protestors and news cameras that they had to be discontinued. Meanwhile, Yellowstone ‘s buffalo herds were swelling, and large groups were leaving on park roads.

As buffalo marched into Montana , state veterinarians and APHIS watched nervously. In 1994 the veterinarians issued a threat: Montana must shoot the incoming buffalo or else test marketable cattle for brucellosis according to their interpretation of federal rules. In response, Montana sued the federal government. The way they saw it, government policies were crippling ranchers. The government allowed diseased buffalo out of Yellowstone , but at the same time punished ranchers when diseased animals entered the surrounding states.

The judge ruled that all parties should stop their squabbling. The state of Montana , the Park, and the federal government needed to work together, divvy up responsibility, and fashion a joint agreement. The result was an interim plan that began in 1996. In the west, state livestock agents would capture and test migrating buffalo, killing those pegged as carriers and releasing the disease-free. In the north, rangers would capture and slaughter all wanderers. In a terrible coincidence, the winter of 1996 was a brutal one, dropping ice on Yellowstone ‘s plateaus and sending the buffalo out in droves. Following convenient adaptations of the plan, livestock agents shot buffalo like a firing squad, and park rangers tested buffalo and let the negative ones go. More than 1,000 buffalo died—some were shot; some were trucked to slaughter; others dropped while on the run, the whole ordeal broadcast on televisions throughout the country.

By 1998 it was time for the agencies to release their final plan for public comment. They stuck with the one drafted after the court case, with a few exceptions. All wandering buffalo would now be tested, negative animals would be vaccinated, and when the herd grew larger than 3,000, all wanderers would be killed.

The Fund for Animals demanded a ban on buffalo capture, killing, and vaccination. Too risky, responded the agencies. A group of state veterinarians and livestock producers asked to ramp up test and slaughter and slash the herd to 1,800. Too aggressive, said the agencies. A diverse group of citizens proposed a more moderate plan—if buffalo would not be confined to park land, why not acquire more land? The Forest Service or public groups could buy ranchers’ fields and turn them over to the buffalo. Too expensive, countered the agencies.

The agencies in the end read the public’s criticisms, weighed the evidence, printed all the comments in voluminous books, and then put the books aside. In 2000, they adopted their plan. The plan still applies today—largely because state and federal agencies cannot agree on anything else.

Read Susan’s entire thesis on MIT’s DSpace

‘If it Quacks Like a Sphere’ — the Million Dollar Problem
Stephen Ornes

It may be impossible to visualize a 3-sphere, but it is possible to explore it. Any system that can be characterized by three numbers automatically determines a three-dimensional shape. Consider the weather as an example. If you take multiple measurements of the temperature, the humidity and the wind speed, you will end up with a collection of data points that are determined by three numbers. These numbers might be thought of as coordinates, and then you’ve determined a “weather shape” that is three-dimensional. In baseball, if you tally the number of runs, number of errors and number of fouls for each inning of a game that doesn’t go into overtime, you have established 9 data points in a three-dimensional space. With those nine points, you could make statements about the “shape” you have created.

You could ask even more complicated questions about the implications of a 3-sphere. What if we lived on the surface of a 3-sphere? If our universe, for example, was a not-too-impossibly-large 3-sphere (a scenario seriously considered by physicists), we’d be able to shoot rockets deep into space, and eventually, the rockets would come back to us from the opposite direction. If you went far enough from where you started, you’d end up where you began.

Now imagine that this 3-sphere universe, like our poor balloon, is distorted, wadded, dilated, and deformed (but not punctured). If we lived in this deformed 3-sphere, then you could feasibly walk across the Golden Gate Bridge and end up on Mars. Or on the event horizon of the massive black hole holding the Milky Way together. You might find yourself on another planet, somewhere in space, where alien beings have such a solid understanding of the topology of the universe that they are not at all surprised to see you.

The Poincaré Conjecture offered a way to identify these blobs as spheres in disguise: it said that if a blob really is a sphere in disguise, then it must be simply connected. In topology, “simply connected” means that you can draw, anywhere on the surface of the thing, a circle, and you can contract that circle to a point. A ping pong ball is simply connected: you can imagine drawing a circle, and shrinking it to down until it was just a dot.

Or, you could think about it this way. You tie a lasso around your blob and tighten it until the string lies on the surface. If, for every different way you can tie the lasso, you can slip it off, then the blob is a sphere. If it is possible to tie the lasso in such a way that it proves impossible to remove the lasso without breaking either the string or the blob, it is not a sphere.

A donut, for example, is not simply connected. It is possible to draw rings on a donut that cannot be contracted. Imagine that an ideal Krispy Kreme delicacy—immediately out of the sugar shower, hot, of course—is a perfect torus. Now imagine a single chocolate ring that begins on the outside of the donut, crests the top of one side, goes through the center hole, and winds up where it began. As delicious as this ring may be, it is impossible to contract. If you tie the lasso through the center of a donut, you cannot remove it without either altering the shape of the donut or cutting the string.

Though this is not its mathematically precise term, ‘breaking the donut’ is absolutely, positively not allowed in the world of topology. You may say that, above all things, topologists respect the donut.

In mathematical terms, the Poincaré Conjecture is that every simply connected 3-dimensional shape is homeomorphic to a 3-sphere. “Homeomorphic,” in this case, means “topologically equivalent”—i.e., indistinguishable to topologists. Spheres in disguise are still spheres. In other words, if you can, without breaking the shape, mold it into another shape, then the two are homeomorphic. A basketball, for example, is homeomorphic to a football. An apple is homeomorphic to an orange.

If an object has a hole that passes all the way through it, then it is not homeomorphic to a sphere. In the class of two dimensional objects that contain one hole, a bicycle tire is homemorphic to a key ring. A coffee cup is homeomorphic to a donut. In fact, a favorite joke among mathematicians is that topologists cannot tell the difference between a coffee cup and a donut.

And this is why Perelman’s story is so compelling. Perelman is not, by training, a topologist. He can distinguish a coffee cup from a donut. But he stepped into the twisted world of topology and found gold on his shoe.

Read Stephen’s entire thesis on MIT’s DSpace

Abandoned Minds:The Escalating Crisis of Geriatric Mental Illness
Michelle Sipics

Alice Weinberg beckons to her daughter and poses a question: "Sally, when is Dad going to get here?" None too spry at 84, Alice ‘s weak voice betrays her age. Still, her frailty is offset by a hopeful smile at the thought of seeing her husband. But there are two problems. Her daughter’s name is not Sally, but Marla – and her husband died 16 years ago.

For Marla, whose mother first began to exhibit symptoms of dementia five years ago, questions like this one have become commonplace. Alice rarely recognizes relatives, and frequently refers to people who have passed away many years before as though they were still alive. In a recent visit, she spoke of an event from Marla’s childhood as if it had happened only days before.

"I don’t know how to talk to her anymore," Marla said.

Alice is far from alone in her affliction. According to a report of the U.S. Surgeon General, the elderly are the most prone of all age groups to mental illness. The National Institute of Mental Health estimates that two million adults over the age of 65 suffer from clinical depression, and as many as five million more have depressive symptoms. Other mental illnesses are prevalent as well, including anxiety disorders, schizophrenia, and Alzheimer’s disease, the 8th leading cause of death in America in 2002 (the last year for which official data are available).

The NIMH also reports that older adults are at a disproportionately high risk for suicide; the Department of Labor lists their age group as having the lowest average income; and the Federal Interagency Forum for Aging Related Statistics reported, not surprisingly, that they have the largest reliance on health care, for which costs are increasing rapidly. Further, according to the U.S. Census Bureau, theirs is the fastest growing age group in the country.

This combination-disproportionately high rates of mental illness in the fastest growing segment of the population-makes the problem one of the most acute in the American health care system. Compounding the problem is the fact that many of today’s elderly grew up in an era that tended to see mental disease as a moral failing, a source of shame to be kept secret from others. Still others write off their symptoms as an inescapable result of old age, not a sign of mental illness. Consequently, relatively few seek help when early intervention could do more good.

"There is a certain stigma attached to the idea of mental illness, especially among older adults," said Jovier Evans, program chief of the Geriatric Translational Neuroscience Program at NIMH. Evans’s program supports the study of late-life mental disorders by the neuro- and cognitive sciences.

Evans added that few elderly individuals would seek help from a mental health practitioner regardless of stigma: "Most older adults don’t seek medical care from specialty clinics, so they wouldn’t see a psychiatrist or psychologist," he said. "They see their primary care physician." Experts cite this fact as one of the reasons mental illnesses are often overlooked in older adults: elderly patients suffering from physical ailments such as fatigue and muscle ache, for example, will generally visit primary care physicians, who are less likely to recognize such complaints as potential symptoms of depression than are psychiatrists or psychologists.

The Alice Weinbergs of this country belong to a large and growing group. According to a 2005 National Institute on Aging report, in 2003, the last year for which figures are available, nearly 36 million people over the age of 65 lived in the U.S. , constituting 12 percent of the population.

That number is expected to soar: the NIA report, called 65+ in the United States : 2005, puts the population of older adults "on the threshold of a boom," projecting a rise to 72 million by the year 2030 – accounting for 20 percent of the U.S. population. The trend is expected to begin in earnest when the first Baby Boomers turn 65 just five years from now, in 2011.

Read Michelle’s entire thesis on MIT’s DSpace