2009 Thesis Excerpts

MacGregor Campbell How to Build a Living Thing

Anne-Marie Corley Reentry

Stephanie Dutchen Lessons From a Rare Disease

Annie Glausser The Placenta's Second Life

Lisa Song Drinking up the Desert

Iris Mónica Vargas Slightly Altered Being

Genevieve Wanucha The Clearest Mirror: The Science of Laughing and Crying

Children with Hutchinson-Gilford progeria syndrome look like strange, haunting hybrids of youth and old age. Like those optical illusions that flip back and forth from a duck to a rabbit, looking at a child with progeria leaves you blinking between a baby and a grandparent. Old and young are supposed to lie at opposite ends of the spectrum, but progeria melds them into one.

Progeria is striking to see. The children's heads look too big for their faces, with visible meandering veins, large eyes, small jaws and beaky noses. They have little or no hair anywhere on their bodies. When they talk—and like any other kids, they talk a lot—it's with voices pitched slightly higher than normal. They're small, often weighing only thirty pounds and standing three feet tall even as teenagers. They have patches of hard or brown skin. Under that skin, much more is going on. The kids lose their body fat—that's what makes their veins look so prominent—and their bones weaken. Their shoulders narrow. The skin and ligaments around their joints stiffen, so they have trouble fully extending their fingers or their knees; problems with their hips leave them walking subtly bowlegged like John Wayne. Most significant of all, they suffer from arteriosclerosis, hardening of the arteries. The resultant strokes or heart attacks eventually kill them. The average life expectancy is thirteen. Some live to be twenty. Some die at three or four.

The children develop normally at first, but by about age two it becomes obvious that they're suffering from what doctors call a failure to thrive: they don't grow enough, no matter how much they eat. Together with hair loss and a vein standing out across the top of the nose, the lack of growth usually leads the doctors to suspect progeria—if they've heard of it. A genetic test confirms the diagnosis.

Progeria is rare, affecting only one in four to eight million people. Forty to fifty children have been diagnosed with progeria in the world right now. In part because of its rarity, no cure or effective treatment has yet been found.

The Office of Rare Diseases Research at the National Institutes of Health defines a rare disease as affecting fewer than two hundred thousand people in the United States . Hemophilia affects eighteen thousand people. Progeria affects twenty people. It is "vanishingly rare," says Bruce Korf, a geneticist at the University of Alabama at Birmingham .

Progeria's rarity can be a problem for the people who want to study it. Researchers have a limited number of tissue samples to examine. When it comes to clinical trials, they can only recruit from a small pool of patients. That number further dwindles because not every family wants to participate, and not all of the children who do are eligible. Those who are accepted don't always survive the full duration. If there are concurrent clinical trials, as there have been since 2008, the available candidates diminish again. And if one trial follows another, the families may begin to suffer from a sort of trial exhaustion, parents less willing to put their children through another rigorous course of therapy that often involves frequent medical examinations and travel. Plus, not all doctors have heard of the disease, so they may incorrectly diagnose affected children. Some researchers estimate that there are four times as many cases of progeria in the world than are currently recognized. This underdiagnosis prevents the kids from getting what help is available and deprives the research community of treasured sources of information.

But there is great potential in persevering despite these obstacles, not only because understanding progeria can lead to a treatment or a cure for the children it strikes, but also because, as most progeria researchers believe, the disease is related to normal human aging.

As I look at the aftermath of this organ, I try to recreate its pre-birth appearance. Where exactly did the baby sit?

To get a sense of this, I start to lift up the sheaths of membrane that formed the amniotic sac. The amniotic sac, while given its own name, is part of the placenta package—the amniotic sheaths could only be separated from the placenta with a sharp knife and steady hands. The placenta is slippery, squirmy even, as it flips inside out, outside in, but I do eventually get a grasp on the sheaths. These paper-thin, stretchy layers are firmly attached around the circumference of the placenta, even though they look flimsy at first glance. When a woman's water breaks, it means that these layers have ruptured and the baby no longer floats within the protected sac membrane.

I hold the sheaths up and it forms a shape similar to the hood of a raincoat, or the entrance to a small round cave. Insert baby here, I tell myself, creating a mental picture of baby-in-utero. Attached to the umbilical cord, the baby sits inside this amniotic cave throughout pregnancy, relying on the interface of the placenta to ferry across its nutrients and oxygen, up through the cord.

The sheaths of the amniotic sac are two-fold. The first layer is the amnion, which is like a clear balloon—sheer, stretchy, and surprisingly strong. If you delicately peel the amnion away (like peeling a fruit roll up from its plastic), then you can separate out the second, outer layer—the chorion. The chorion has knobbles on its thin surface and feels rather like plucked chicken skin. It is a watercolor of blood red and fleshy tones. When I hold it up, light can still shine through it.

I let the amniotic membranes collapse and try to visualize the insides of this thick placenta pancake. The exchange of blood that occurs here is a remarkable feat of human evolution—the mother can provide a host of life-sustaining nutrients and gases to the fetus, all without ever directly swapping blood (a necessary feature considering the variations in maternal and fetal blood types, and the severe consequences of mixing unmatched blood). The placenta is filled with the branching roots of the chorionic villi, which house the tiniest of the fetal blood vessels. These villi feed into the bulging blood vessels I could feel on the fetal surface, which then funnel into the umbilical cord.

Maternal blood, carrying nutrients, flows into the inner portion of the placenta, bathing the villi. What makes the process so special, though, is the outer layer of the villi—the syncytiotrophoblast. It's a clunky word, but its function is rather beautiful. Dr. Michael Nelson, OBGYN at Washington University School of Medicine and editor of the journal Placenta , first introduced me to the uniqueness of the syncytiotrophoblast. It is an outer cell layer that is one continuous structure, as compared to traditional outer cell layers that are divided cell by cell. “Try thinking of cells as bricks,” Nelson said to me—if you just lined up your bricks and it rained, water would get through the cracks. But if you pour concrete to fill in the gaps between the bricks, no water gets through because it is one continuous mass. The syncytiotrophoblast is like bricks with concrete: no gaps between cells, just one continuous cytoplasm that holds multiple nuclei. This means that everything has to be transported across the expanse of the 'blast; there are no cracks for blood droplets to leak in.

Tucson is the kind of desert you want to own. When the sun slides over the majestic saguaro cacti and the roadrunners hop like ungainly stilt-walkers, it's hard not to imagine claiming a slice of it for yourself. These are not the sand dunes of the Sahara; Tucson lies in the midst of the Sonoran Desert, a surprisingly lush landscape that extends far beyond the city limits. There's space out here, and it's easy to build a house on the edge of town, to pave the driveway but leave the backyard in its natural state. Soon the wildlife appear: woodpeckers and javelinas, lizards and quail. In springtime the ocotillos start blooming, flower buds tapered like orange asparagus tips. By fall the hummingbirds wobble drunkenly in flight, drugged on fermented saguaro fruit. Except for brief monsoons that dump water from the sky, turning the land into a vibrant field of wildflowers, the weather stays sunny and dry year-round. All is well, until the neighbors move in.

One morning the view out the back porch is blocked by another house, part of a new subdivision just two blocks further into the desert. That house marks the new boundary of the city—for a little while, at least. The money is in the dirt, runs the age-old mantra of development. And the dirt is cheaper at the edge.

Many who move to Tucson end up destroying the desert isolation they came for. David Taylor, one of the city's demographic advisors, says “We're schizophrenic about growth. When we're at work we're for more sales, bigger staff. In the driveway coming home at night we're for fewer people scaring their quail, blocking their view.”

As one of the fastest-growing cities in America, Tucson suffers from a classic case of urban sprawl. “Drive ‘till you qualify” is the slogan for those seeking affordable homes far from the urban center, yet close enough for daily commutes. From any hilltop one can see the city spread out like a bulging amoeba, a staggering mass of retail stores and flat, adobe-style homes. The roads seem to go on forever, curving up over the horizon. Back in 1998, twelve acres of desert a day were bladed down, bulldozed under and paved for new development. Throughout Tucson and surrounding Pima County, developers submitted plans for enormous subdivisions on pristine desert lands, and with few exceptions, the County Board of Supervisors approved them all.

…

Everyone wants a piece of desert. The frontier dream of a home among the saguaros is the draw of Tucson. “People move in,” said Susannah Brown, a college student who grew up in the city suburbs. “Then they want to protect the desert and don't want anyone else to come.”

As water futures dwindle and desert lands disappear under pavement, that dream will soon be over. For all its efforts, Tucson's conservation measures are beset by loopholes: the Sonoran Desert plan has no way of halting growth, the replenishment district replaces groundwater to little effect—and that's not to mention the outer world beyond Pima County's control. “The Sun Corridor is going to happen,” urban planner Changkakoti predicted grimly, referring to the day thirty or fifty years from now when Phoenix and Tucson will join to form one massive metropolis. “The question is, how?” Will it be a series of densely-populated urban centers or subdivisions that take over every corner of the desert? “You cannot stretch out single family homes on one-acre lots until kingdom come and declare victory under the banner of the Sun Corridor,” warned Changkakoti. It would be the end of the Sonoran Desert as we know it. “You'll end up with a moonscape.”

*

When the pygmy owl flew away, Richardson and I drove back to town in near silence. I felt strangely honored by the bird's presence; I did not expect to ever see another. Outside the car, desert plain gave way to tumble-down trailers and the weekday rush-hour traffic speeding by, mere minutes from the owls' nests. Tucson was once the place where you could get it all: sunshine and spacious homes, clean water and saguaros on your doorstep—but no longer. Something has to give: will the same people who rallied for the pygmy owls suffer to live in dense urban housing and pay to drink reclaimed water?

“I used to think there were warring camps,” said David Taylor. “Land developers who schemed great schemes about how raw desert could be turned into housing…and [in the] other crowd a sea of plaid, Birkenstock and hair, people who wanted to retreat to the Pleistocene, make everything go away…in fact those polar views exist in all of us, individually.”