2009 Thesis Excerpts
How to Build a Living Thing
by MacGregor Campbell
A translucent hairy pickle, visible only under the microscope, Tetrahymena thermophilia spends its days floating in temperate bodies of freshwater, motoring around with its thousands of tiny hairs, snacking on passing bits of debris. Most people wouldn’t distinguish it from pond scum because it is, in fact, pond scum.
To scientists, however, this little protozoan has yielded critical secrets about how life works. In the early 1980s it told a young researcher at the University of Colorado named Thomas Cech what might turn out to be the biggest one of all. It used to be assumed that cells observed a strict division between Labor and Management. DNA knew what to do; complex molecular machines called ribosomes knew how to do it. In 1980, everybody knew that RNA was just a messenger, a molecular errand-boy relaying instructions from DNA in a cell’s nucleus to the ribosomes in charge of making the larger molecules required to keep a cell alive. The intricate work of the cell was handled by protein enzymes, twisty, folded molecules whose physical shape allows them to facilitate otherwise unlikely chemical reactions.
But with T. thermophilia’s help, Cech discovered that such strict division of labor did not always hold in nature. He found that some strands of T. thermophilia’s RNA could snip off pieces of themselves without the help of proteins. This humble reaction turned molecular biology on its head: now enzymes weren’t limited to being made of proteins, they could be made of RNA. Cech and Sidney Altman–who found a similar phenomenon at Yale–won the 1989 Nobel Prize for Chemistry, for this discovery.
With the ability to both store information and catalyze reactions, the possibility arose that RNA might be a biological entrepreneur, simultaneously directing and carrying out the functions of a simple cell. Life based solely on RNA became a feasible idea, though it had never been observed before in nature. Many began to believe that RNA-based life might have preceded the current world of DNA, RNA, and proteins. Nobel Laureate Walter Gilbert coined the term "RNA world" in 1986 to describe such a primordial Earth.
Origins researchers imagined seas, or at least pools, of RNA molecules having different properties, undergoing a form of molecular evolution. Some molecules might be active enough to make copies of themselves. These would have an advantage, population-wise, over molecules that couldn’t. Mutations that led to better replication would drive evolution and set in motion the chain of events that billions of years later would lead to dogs and human beings.
The problem is that all of this would have happened somewhere around 3.5 to four billion years ago. Scientists believe that fossil evidence of the event would have long been destroyed. This leaves two options for anyone interested in figuring out how life might have started on Earth. The first is to look at the geological record and speculate about what chemicals might have been present, what the early oceans were like, what the atmosphere was like, and imagine possible chemical routes to life. The second is to put on the lab coat and safety goggles and actually try to make it happen right now.
Cech’s discovery of ribozymes hinted that this second approach might be feasible. A little less than twenty years after the breakthrough, a group of scientists who had been working on origins of life problems, Jack Szostak of the Howard Hughes Medical Institute, David Bartel of MIT’s Whitehead Laboratory, and Pier Luigi Luisi of the Institut fOr Polymere in Switzerland set out to see just how powerful a ribozyme might be. They called their shot in a January 2001 issue of the journal Nature, laying out a roadmap to build a simple primitive cell-a protocell. The paper was called "Synthesizing Life", and in it they claimed it would be possible for humans to do what had never been done before: build a living thing, from scratch, in the laboratory.
“Reentry” most often evokes an image of the space shuttle flying through earth’s atmosphere, glowing hot from friction, then landing on the runway and rolling to a halt. By then, the astronauts’ job is finished. The hard part is over. Adjusting after six months in space, or even two weeks, should be a snap. After all, astronauts spend almost their entire lives on earth. But when the shuttle touches down at Kennedy Space Center or Edwards Air Force Base; when the parachutes fly; when the kids ask mom or dad if dad or mom is really coming home; when the astronauts lift their arms and feel them as heavy as a ship’s anchor; when the mission is officially complete; the journey isn’t over. The real reentry begins at wheel stop.
Gravity hits them first. Astronauts cope with intense physical changes on earth after getting used to living weightless in space. Then come the more subtle problems. After weeks or months away from home, astronauts have to work to reintegrate back into their families. At the same time, they’re traveling to tell their story to the world. And they have to deal with the psychological challenges of no longer being “number one,” NASA’s main squeeze; by the time they get back, new space crews have taken their place as top priority for NASA and the press. Like reverse culture shock, re-immersion in the native environment of earth can be more disorienting than leaving in the first place.
In the cradle days of extraterrestrial travel, researchers didn’t know if humans could even survive for long periods of time in micrograv ity, the “zero-g” environment of the vacuum of space. Yuri Gagarin, Alan Shepard, and their contemporaries rocketed into space for minutes or hours at a time, a day or two at most. Longer missions sent astronauts home tired and weak, unable to function as well as they had before they left. Indeed, when Russian cosmonauts had to be carried out of their space capsules on stretchers, concerns for human adaptability seemed justified. But the problem wasn’t in adapting to space. That part the human body mastered. The problem, it turned out, was in coming back to earth.
On his first day home from the International Space Station, Mike Lopez-Alegria gripped the wall. If he closed his eyes, he thought, he would fall down. He couldn’t tell without looking which way was up.
One of the hardest experiences of Greg Chamitoff’s life was trying to get from the bed to the bathroom. He crawled. He tumbled. He crawled some more. He struggled with every inch of progress. Gravity was pinning him down.
Jeff Hoffman lay on his back in bed. Just returned from his first of five Space Shuttle flights, he was feeling pretty good. He relaxed his arms and legs. He closed his eyes in the dark, as previous fliers had told him to do. For a moment, he could have sworn he was floating in space.
Rick Linnehan woke up his first morning back feeling weightless. He rolled over to get up, as he had every morning on the shuttle. He fell flat on his face.
Lessons From a Rare Disease
by Stephanie Dutchen
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.
The Placenta’s Second Life
by Annie Glausser
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.
Drinking Up the Desert
by Lisa Song
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.”
Earthlings: Humanity’s Essential Relationship with Gravity
Iris Mónica Vargas
Remember that instant when, as you ran around the shadows of imaginary jungles in your backyard, falling once and tripping twice, your gaze was caught by a fragile silky web with a tiny spider in the middle? You were mesmerized by the steady weaving of its many limbs –it would not easily fall down- simply swaying to and swaying fro, laboriously spinning and laying the symmetry of its web in what seemed to you such a magical, private moment -as though you were observing an ancient secret.
I was a child fascinated with space. The untamed and unsophisticated backyard of our humble house in the rural Barrio Bajuras in Puerto Rico contained an entire universe within it. At night it was the most comfortable seat for watching the grand opera of the skies, imbued with the aroma and consistency of dewed soil. During the day, hiding among branches and leaves and passion fruit vines, the handy-work of a single spider on the termite-ridden poles on which our zinc roof rested would transfix me. The fabric of its creation, the geometry of its silky space, would make me ponder what it was like to be her, that tiny spider, to live in her world, do what she did, and see what she saw. Did she see me as distant as all the cosmic bodies I saw in the night-sky? Was I as mysterious, as unrelated to her everyday life as that sparkling vault was to me? How come she always knew exactly where to weave her next thread? How come her threads were always so perfect, so symmetrical? What was telling her to spin as she did? If she were somewhere else, some far away world, would she still go about her routine, weaving her space fabric like she always did? As a curious child, I wondered what it would be like for a spider to live up on the Moon, or on another planet, another galaxy even.
Within the warmth of my tropical island backyard, I thought the Universe was the extension of my barrio, one welcoming fabric, seamless in its extension. I wondered if other creatures existed, within the vastness of space, that were different from me. Could they jump higher than I could? Would they look different than the tadpoles around me? Sing brighter than my coquies, my tiny Puerto Rican frogs? I daydreamed about how everything and everyone else around me would behave when surrounded by the darkness and the vastness of space. What would space feel like to me? Could it make me feel freer, and would my backyard spider still be able to weave her web? Would it adapt to its new backyard? When witnessing the perfection of that tiny spider’s craft, I wondered if she would still know what to do when no longer an Earthling.
Anita and Arabella went to space in 1973. That was before I was even born. In her very own yard, 2,684 kilometers from my tropical Caribbean island, and thirteen years before I started daydreaming about it, a young girl by the name of Judy Miles had been wondering too, whether spiders could spin their silky webs in the near-weightlessness of space. Judy was a high school student from Lexington, Massachusetts who managed to send her query up to space where astronaut Owen Garriot released two female cross spiders (Araneus diadematus), the first world spidemauts, Anita and Arabella, into a box similar to a window frame, near which a camera would recorded their spider activities aboard Skylab.
On July 28, 1973, space met two shy creatures unwilling to exit their space capsule -a storage vial with a water-soaked sponge to maintain them hydrated. Their erratic ‘swimming motions’ as they finally emerged from their capsules into the experiment cages, conveyed a struggle to adapt to the strange new environment they had been brought into.
Arabella was the first to decide that life had to go on. On the day after her arrival in space, she weaved a rudimentary web in a comer of her box -the first web ever spun in space. The following day she completed her work. Arabella’s ability to cope with her new surroundings impressed everyone. On August 13, wanting to see whether Arabella was capable of repeating her feat, astronauts removed half of her web. At first, she didn’t seem to fancy entertaining anybody’s whims. When Arabella finally set herself to the task, she consumed the remaining half of her web, and began moving in circular patterns. The resulting web was more symmetrical than the first.
Perhaps because of the stress of their new environment (spiders have been known to behave abnormally under stressful conditions) neither Arabella’s nor Anita’s silk was like that they had produced on Earth. Some parts of their webs were thinner than others. Even the angles of their radial threads were unlike those on Earth. Although Arabella and Anita were able to spin webs in microgravity, they never performed exactly as they had done before they went to space.
The Clearest Mirror: The Science of Laughing and Crying
At 7:15pm, the tiny yellow light bulbs dotting the ceiling of London’s Lyttelton Theatre dimmed slowly over the audience. Solid black replaced the waning starlight. Eight hundred and ninety pairs of eyeballs followed the same dark trajectory, looking forward in simultaneous, directed blindness. The play, Tracy Letts’s August: Osage County, had just won five Tony awards and the 2008 Pulitzer Prize for best drama. The three-hour-and-twenty- minute tragicomedy of a Mid-western family’s loud dysfunction spilling addiction, psychological degeneration, incest, suicide, and racism into the theatre was "the first great American play of the 21st century," according to theatre critics. Now it had come to the Lyttelton, tucked into the northwest wing of the National Theatre. Anticipation thickened the air, a silent, collective creation. The man in 6A in the front row cleared his throat and thumbed the velvet fibers of his armrest as the black slats of the metal curtain slowly climbed upward in smooth horizontal folds to expose the interior of a fully-furnished, three-floored Oklahoma house.
Deep within the 2.95-pound rubbery, tightly folded mass inside the head of the man in 6A, a nerve fiber, or neuron, twitched, zapping a connected nerve fiber, and passed an electrical signal down 20 nanometers to the next neuron. Actor Paul Vincent O’Connor sat under the gold glow of the floodlights, swigging whiskey and drunkenly quoting T.S Eliot. "My wife takes pills and I drink, O’Connor said nonchalantly to the new housekeeper. "…That’s the bargain we’ve struck."
The orbicular muscles encircling the eyeballs of the man in 6A received the traveling electric pulses and slowly crunched tight beneath wrinkled skin, pulling inward his cheeks and forehead. Zygomatic muscles, anchored at each cheekbone like leathery strings attached to a marionette, tugged the comers of his mouth backwards and up.
"Oh God, they’re called Native Americans now, Mom!" actress Amy Morton groaned, scowling.
"Who makes that decision?"
"It’s what they like to be called!"
"They’re not anymore native than me!"
"In fact they are."
A sudden cough-like 310-millisecond long noise exploded from the throat of the man in 6A, extending to a frequency of 10,000 Hertz. Five smaller pulses beginning with the /h/ sound followed, hovering around 6 Hertz each, lasting 1/15 second and repeating every 1/5 second. The soft tissue lining his upper larynx vibrated 120 times per second. His heart pumped faster, its rate increasing to 115 beats per minute as the words’ impact settled. His lungs expelled air in fast bursts and then violently sucked it back to avoid suffocation. Oxygen level remained constant. Blood vessels relaxed. Some of the one billion neurons in his spinal cord slowly calmed down, softening muscle tone. Endogenous opioids, the body’s natural painkillers, leaked from a spindly protrusion of a neuron to the next, and then trickled into his bloodstream. His abdominal muscles clenched in rhythmic spasms. A sudden decrease in the activity of neurons sending signals to his tibial nerves, fibrous tubes running down the back of the knees to the sole of the feet, temporarily paralyzed muscles of both legs.
"I think you should try to prepare your wife if you can," the sheriff told Perry.
Viewers in the front row seats could almost feel the spit popping out of the two
"What happens to a body," the thespian sheriff told Perry. "It’s very bloated, an ugly color. And fish have eaten the eyes."
"Oh Christ. How does a person jump in the water…and choose not to swim?"
"I don’t think you do unless you really mean business."
Perry stood, face blank, lights dimming, and repeated, "Choose not to swim."
Hit with the electric signal sent from a bulb at the top of his brainstem, the lacrimal gland of the man in 6A, a puffy packet of cells perched on top on his eyeballs in the bony space behind the eyebrows, began to produce a salty liquid. This warm liquid flowed into small drains called puncta, permanent 0.2 to 0.3 millimeter openings in the papilla lacrimalis, the pink triangle of tissue where his morning eye grit collected. A small amount of this liquid, swimming with globins, glucose, antimicrobial agents, lipids, endorphins, urea, potassium, manganese and sodium, passed through the puncta into another bundle of tissues, the lacrimal sac, then pushed past a membranous flap, the Valve of Hasner. Tiny tubuloalveolar glands secreted streams of phlegm. The thick solution emptied into the nasal passages. The immune enzyme lysozyme in this liquid killed a few of the Streptococcus bacteria swarming along the pseudo stratified columnar epithelia lining the inside of his nostrils. He reached for a tissue. The rest of the fluid dripping from the top of the eye quickly expanded in volume as he continued to watch the expression on Perry’s face, and overwhelmed the tiny pink puncta, which could only drain at the rate of a micro-liter and a half per minute. The trembling ledges of eyelids kicked over a drop. He blinked and swallowed. From where I sat in seat 7A, I saw him press a finger hard to the bridge of his nose, and begin to cry.