2005 Thesis Excerpts
Monica Bobra The Endless Mantra: Innovation at the Keck Observatory
Jenny Boyce Scroop, Luster, and Hand: the Science and Sensuality of Silk
Kevin Bullis When Machines Touch Back: Simulating–and Stimulating–the Most Intimate of Senses
Emily Kagan Cancer and the Clock
Maureen McDonough Barren Promise: The Hope and Heartache in Treating Infertility
Siri Lefren Steiner The Natural History of a Lost Sense
Sixteen minutes and eight and a half seconds after midnight, Hawaiian Standard Time, on that much-anticipated day, the European-engineered Huygens probe sank into Titan’s atmosphere. Named after the Dutch astronomer Christiaan Huygens, who discovered Titan in 1655, the robotic Huygens probe used its six instruments to make as many atmospheric measurements as possible within its three hours of battery life.
Friction between the probe’s heat shield and Titan’s atmosphere was expected to create a bright fireball lasting up to thirty seconds. And although it was night on Earth during Huygen’s descent, it was mid-day on Titan where the probe was to land. Keck astronomers predicted the probe’s fireball to be as bright as Titan’s clouds, hopefully causing just one pixel to flare to an intensity twice as bright as the cloudcover….
As photons from Titan spill into the Keck Observatory’s adaptive optics system, they embark on a journey just as complicated as their trek through the atmosphere. The photons bounce from one instrument to another in a manner reminiscent of George Rhoads’ Archimedean Excogitation, a sculpture in the Boston Museum of Science. His 27-foot tall tower features bilhard balls flying down ramps, turning gears, whirring wheels, and flipping levers before coming to their final resting place.
Photons also bound off several instruments in an adaptive optics system. After they hit the primary mirror, the photons are directed onto a tip-tilt mirror, which moves back and forth on one axis to correct waves of light that are evenly spaced and parallel but arriving at different angles.
After the photons leave the tip-tilt mirror, they hit a device known as a deformable mirror. This frisbee-sized device continually flexes into the opposite shape as the incoming light waves. As a result, light waves bouncing off its surface straighten out.
The photons continue their journey. They hit a parabolic mirror — known as a collimator — which channels the light into a long, straight column. This column is directed into a dichroic, also known as a beamsplitter, which separates the light beam into visible and infrared wavelengths. The visible light enters an instrument that analyzes it; the infrared light enters the camera.
The visible-light photons enter a Shack-Hartmann wavefront sensor, which is an array of tiny lenses that evenly separates the photons to create 400 individual images of Titan. Each image is smaller than the bundles of light falling onto the telescope. In this way, the wavefront sensor catches each bundle like a strainer catching pasta. If the wavefront sensor’s images were bigger than the bundles, some bundles of light might pass through, uncorrected, like fettuccini slipping through a large-holed strainer.
Each lens has a property termed the centroid, which measures how off-center the image is: too far up, down, left, or right. A computer analyzes this information and translates the data into a three-dimensional Zernike function; mathematically, a Zernike function looks like a congested combination of cosine and sine waves mixed with high order polynomials. Graphically, it looks like a potato chip.
This information from the wavefront sensor is cycled back to the deformable mirror, which then adjusts its shape to model the Zernike function. In this way. the wavefront sensor continually drives the deformable mirror, which reads in data up to 670 times a second and subtly changes its shape every time. It must work faster than the smallest changes in the atmosphere’s movement, or coherence time. If the deformable imrror works too slowly, photons will jostle around midway through the correction. This will eventually produce a blurry image, much like the elongated lines of light created during a long-exposure photograph of speeding cars.
The infrared-light photons, meanwhile, travel into the camera — now fully laundered by the deformable mirror and ready to produce a crisp image….
[Al] Conrad went into this office to clean up some of the images, subtracting background radiation from the Earth’s upper atmosphere and from the telescope’s instruments….[He] printed out a picture and brought it into the control room, pointing to a spot in Titan’s southern hemisphere.
Most of the bystanders spent a few silent minutes looking at a perfectly uniform, though otherwise magnificent, picture of the distant moon. They quietly dispersed. It had been a long, stressful day. Despite the disappointment, the idea that one could hope to see something as big as a bonfire some billion kilometers away is a monument to adaptive optics.
Over the thousands of years and thousands of insect generations that humans have been cultivating Bombyx mori, the silkworm has become entirely domesticated, no longer able to survive without constant human attention. Although the adult moth has wings, it has lost the ability to fly, probably as a result of selective breeding of ever-larger individuals. It is blind in the pre-cocoon caterpillar stage, the longest of its life. Perhaps not surprisingly, though a silkworm is blind, it has an exquisite sensitivity to noise. Startled by sudden or sharp noises, it may stop feeding and prematurely discharge the gooey liquid that should have been extruded as silk later on. An event as loud and long as a thunderstorm can significantly reduce the yield for the season.
To move any distance the silkworm must be carried. It is incapable of foraging for mulberry leaves (a silkworm’s lifelong diet), which humans must supply— freshly picked and chopped, to save the lazy things the trouble of gnawing on whole leaves. When it is time to spin the cocoon, the silkworm sometimes can’t even find a suitable branch or twig to attach it to on its own; it must be placed on one by hand.
A Bombyx silkmoth begins its indolent life as one of hundreds of eggs laid by a single adult female on any available surface, including her own cocoon. Incubation of la graine takes about ten days. It is an indication of how important silk-rearing was to some rural economies in Europe, not so long ago, that women frequently incubated the eggs in specially made pouches hung between their breasts to maintain the proper temperature. Newly-hatched caterpillars are too small to be picked up by human fingers, but not for long. Their appetites are insatiable; the caterpillars eat so much so quickly that the sound of their chewing and the constant fall of the tremendous volume of droppings produced—the frass—has been likened to the patter of raindrops on a forest canopy. This feeding frenzy supplies the fuel for the astonishing growth spurt to come.
Four weeks later, the fully grown blue-white caterpillar is nearly as thick, and at least as long, as a human adult’s finger; its body weight has increased 10,000-fold since it hatched. At this rate, it rapidly outgrows its own skin, and must molt four times within its short larval stage, a process known as ecdysis. As molting time approaches, the caterpillar stops eating for a day or two, then rears up on its hind legs, holding this position for several days. Since an entire generation of silkworms hatches at approximately the same time, they reach the molting stage roughly in unison, as well. Imagine the sight—rooms filled with tray upon tray of pallid, corpulent caterpillars frozen in this grotesque insect asana.
Eventually the too-tight skin splits along the nose, allowing the creature to wriggle out, ravenous and eager to make up for lost eating time. Three more times it poses and sheds its skin before it has eaten enough and can get down to business—the spinning of the cocoon.
The caterpillar’s essential equipment consists of two bags of sticky fluid, one down each side of its body, and two openings beneath its lower lip. The liquid hits the air and is oxidized, only then becoming the unique fiber we recognize as silk. Like a spider spinning a web, the silkworm first constructs a silk framework on which to build the rest of the cocoon. Then, moving its head in a figure-eight motion, it spins the outer layers first. Continuing to spin from the inside, the caterpillar entombs itself as deeply as its silk supply allows.
Though the silkworm doesn’t know it, “entombment” is not just a metaphor. In nature, when its metamorphosis from caterpillar to adult is complete, the moth is ready to break out of its cocoon. Its mouth produces an enzyme which dissolves one end of the cocoon, cutting a moth-sized escape hatch. Cocoons must be intact as they are unwound, so to prevent their emergence the silkworms must be “stifled”—a polite way of saying killed—to harvest the silk. There are several methods of stifling: baking the cocoons, steaming them, leaving them out in the sun, even freezing them. “One New England farmer suggested steaming them with rum. Maybe he thought it would put them to sleep in a gentler way,” Dr. Senechal tells me. Silkworms might like that; it seems to suit their lethargic nature and indolent life-style.
The modern era of haptics research began, arguably, in a sixth-grade classroom at the Lewis County Central Elementary School in Vanceburg , Kentucky . The year was 1982. In that classroom, Thomas Massie, who would go on to invent the Phantom, decided he wanted to build a robot. Soon after he thought of a purpose for the robot. He needed help cleaning up the clutter in his room, a problem that, not surprisingly, became more serious once he got started on his project. Massie’s ambition made him a menace to household electronics. His toys never survived long intact, and once apart, they were done for, at least for their intended purpose. “They were usually terminal autopsies,” he told me many years later.
Every year at Christmas Massie’s mother would put out a lawn decoration that his father had acquired as a beer salesman. Stroh’s beer marketers had devised a clever advertisement in the form of a rotating “Stroh-man,” a beer-loving snowman. The winter after Massie decided to build a robot, his mother was furious to find the Stroh-man inoperable. Massie had scavenged its electric motor.
Because of his interest in hands, and because he had no idea how he’d give the robot a brain or eyes, Massie started his robot project with the arm. In addition to “cannibalizing,” as he put it, the Stroh-man, he used gears from a broken clock to make the wrist, motors from toy “tumble-buggies” to power the shoulder and elbow, a thread spool for the palm, lead tire weights to counterbalance the arm and make it easier to control with the motors, and various pieces of salvaged metal. He used the motor from the Stroh-man to open and close a pincer-like hand.
At first, the arm didn’t work. He had designed the arrangement of joints based on what he could observe about his own arm and hand. The tendons he saw moving beneath his skin reminded him of rubber bands, so he used these to connect the motors to the arm segments. But the bands stretched as the motors wound them up, especially when the arm was trying to lift something. They tightened without moving the object until they suddenly sprung, flinging the object dangerously and destroying the arm. An interesting catapult, but not the best system for organizing the room. He replaced the rubber bands with string, entered the machine in a science fair, and won.
Massie entered robot arms in science fairs every year from then until his junior year in high school. His eighth-grade robots used light sensors from a toy shooting game. Since his mother managed to keep him from taking apart the family’s new PC Junior, he had to find an indirect way to use the computer to control the arm. He taped the light sensors to a computer monitor and wrote a program that displayed white boxes arrayed across the screen. These boxes activated the sensors and relayed signals to the arm. This ingenuity helped send him to an international science fair in Texas .
When he got there, his rag-tag invention and magic-marker posters seemed totally out-classed. Seeing the competition, even the teacher who came with him, and who had taken extra time to encourage Massie’s projects, was so sure the young man had no chance of winning that he stayed behind in the hotel during the awards ceremony. Massie only went to the ceremony to find out who won and to get a look at the winning entries.
Ben “Bebba” Woods was a big man — his thick frame offset by a baby face and disarming smile. He was stubborn, strong and accustomed to hard times. Having survived the Holocaust, he was a man who knew pain and he confronted it with a quiet stoicism. Yet even his grandchildren could read the twisted expressions of pain on his face as he battled stomach cancer. He was undergoing chemotherapy, but the toxins that ran through his body were careless assassins, ravaging healthy and cancerous cells alike. They had destroyed his appetite, sense of smell and taste, and left him short of breath. Worse yet, the drugs failed to defeat the cancer.
Across the country in a University of Minnesota research lab, a mouse was undergoing a similar treatment. But this mouse, pumped full of a comparable amount of chemotherapy drugs, was doing far better than Bebba. The mouse suffered from fewer side effects and was able to tolerate even higher doses of the chemotherapy than expected. Most importantly, its tumors were shrinking.
There was nothing particularly special about this mouse. The drugs it was given, 5-FU and leucovorin, were the identical FDA approved drugs that were being administered to human patients at cancer treatment facilities across the country. The drugs were given tot he mouse in doses proportional to what a man of Bebba’s size would have received, and with the same frequency. The only difference between the treatment that failed Bebba Woods and the one that saved the mouse was the time of day.
About fifty years ago scientists started noticing that our body’s biological rhythms did a whole lot more than govern our sleep-wake cycles. Their research found that internal, biological clocks regulate just about every process that takes place in our bodies. While the part of yourself called “me” performs the temporal gymnastics of waking up, getting to work on time, picking up the kids and cooking dinner, your body cycles on and off a myriad of different processes like metabolism, blood pressure, hormone levels and immune response. With this deepening understanding of biological time-keeping came the idea that these rhythms must affect how the body responds to drugs administered over the course of the day.
Several thousand rats and mice later, researchers had discovered that drugs did indeed behave differently over a 24-hour span; at certain times they were spectacularly more effective and had far fewer toxic side effects. This concept was dubbed chronotheraphy ( chrono from the Latin word for time).
The logic ran from rodents to people. “We know that every cell in the human body has a clock,” said oncologist Bill Hrushesky of the University of South Carolina, chronotherapy’s leading advocate. “Furthermore, clocks regulate the functions of all the tissues in our body, including neoplastic (tumor) tissue…” That fact frames chronotherapy’s fundamental premise: specifying the time when a drug should be given could have a significant impact in the care of human illness – especially cancer, a disease notorious for its punishing and often ineffective treatments.
After eleven years, five states, five miscarriages, and two IVF cycles, Devina and Barry are still not pregnant. Yet, they have hope.
Their journey with infertility began shortly after they were married, when Devina was diagnosed with endometriosis and her doctor told her that if she wanted children, she should try to get pregnant as soon as possible.
“Do it while you can,” Devina recalls with a smile. “So basically we’ve been trying for eleven years.”
But while Devina and Barry became pregnant on their own approximately once every two years, those pregnancies always ended in miscarriage. When they first started seeking treatment they were living in Arizona, which doesn’t require insurance companies to cover IVF. They did the treatments they could afford, which included intrauterine insemination and drugs that would stimulate ovulation. While waiting month after month to see if Devina would become pregnant, the couple also began to slowly save up the $9,000 to $17,000 it would cost to try a single cycle of IVF. That’s one egg retrieval, one batch of fertilizations, and one embryo transfer. Their journey continued in the same vein from Washington to Iowa to Texas. Where no IVF insurance coverage is mandated, none is provided. They continued to save.
When Devina and Barry moved to Massachusetts they were thrilled to discover that the state requires insurance companies to cover IVF. Devina braved the shots, the blood draws, the exams, and the surgery to finally try IVF. She got pregnant, and then miscarried.
Following her doctor’s recommendation, they tried IVF again, but this time with PGD. Before the embryos were transferred back into Devina, PGD was used to look for chromosomal abnormalities in the biopsied cells.
Four embryos were produced from that round of IVF, and one cell from each was sent to West Orange, New Jersey. The results came back. One had no genetic material at all, but that might have been because it was lost in the biopsy process. The second had only one X chromosome and no Y chromosome and would have led to miscarriage if it had been transferred. The third would have also failed because it had two X chromosomes and one Y chromosome. The last one was normal and had the sex chromosomes of XY. They had one normal embryo.
“When they said [our only normal embryo] was XY, I looked at my husband and said that means it’s a boy. The smile that came over his face I will never forget,” recalled Devina. I’m sure that he would have had that same smile if it was a girl, but he just kept repeating over and over for a couple of minutes ‘so it’s a boy, so it’s a boy.’”
When Devina became pregnant, the couple thought, “This is it.” Finally they were going to become parents.
“We felt very hopeful because the way that it was described was that if there was a genetically normal embryo that there would only be a ten percent chance of miscarriage,” says Devina. In reality, according to Dr. Scott, patients like Devina have a much higher chance of miscarriage then ten percent, even with PGD. This shows the danger in giving patients a new technology into which they can invest all of their hope. When patients are in such a precarious position, it’s very easy for them to latch onto wrong information.
“I know in my mind that it’s not a baby,” Devina says. “I know this. But when you see that embryo being transferred into your uterus, it’s like, oh my god, there’s my child. I know that it’s not logical, but it’s just an over whelming feeling. Maybe it’s just the well of hope—it’s just so full.”
But, yet again, the pregnancy ended in miscarriage.
In reviewing her medical history, her doctors realized that a routine test had not been done. There is a correlation between recurrent miscarriage and a blood-clotting factor caused by a genetic trait called the Prothrombin gene mutation. A simple and routine genetic test, which had been overlooked, was then conducted. Devina carried the mutation. If she had been taking a drug called heparin, which prevents blood from over-clotting before and during her pregnancy, she may not have miscarried. Barry was furious. Devina was distraught.
Take ants. Most of us have seen lines of them, marching from nowhere. Tidy and single file, they can wind under the kitchen door, hang a left at the linoleum, disappear behind the refrigerator, re-emerge at the base of the cabinet, march vertically at an inconceivable ninety degree angle, continue up the crevice where the walls meet, make a non-sense semi-circle, and then, with aggravating innocence, arrive at the drips that cling to the already crowded plastic honey-bear in the cupboard.
How do such tiny beings see the long, winding route from the nest to the honey? They don’t. Unlike humans, ants don’t rely on sight for most of their information. They use pheromones. Ants leave the nest and spread in different directions, scouting for food. Like Hansel and Gretel’s breadcrumbs, the scouting ants leave a light trail of pheromones they can follow back to the nest. This trail evaporates rapidly, so ants don’t dilly-dally. Once an ant finds food, he drags his behind all the way back to the nest, releasing a heavier trail back to the food. Other ants in his community are recruited. Without knowing exactly where it leads, they follow the chemical road. As they go, they lay down more pheromones, making the path even more obvious. More ants come to feast and carry bits back to the nest. Eventually, the food source is depleted and the ants stop laying track. Without re-enforcement, the trail evaporates and ants start scouting all over again.
For many insects, pheromones help organize communities. “Honeybees put pheromones in their honey in order to communicate,” said John Ascher, a bee expert at the Museum of Natural History in New York. “They don’t just use it for food. It’s amazing how quickly it can spread messages.” These powerful chemicals keep the hive running smoothly. Honeybee hives, for instance, only have one reproducing female—the queen. The rest are workers, who are not able to reach sexual maturity because the queen releases pheromones that make them labor with the drones. They work and die to keep the queen comfortable and fertile, but if the pheromones didn’t exist, they would also mature, develop eggs, and get lazy.
Moths rely on pheromones for love. Males have feathery antennae for detecting the female perfume. The females don’t fly, but can call the males to them from nearly five kilometers away. Some clever moth-hungry spiders mimic these strong pheromones. Like an addict who risks his life for a fix, the male moth flies to the spider, eventually falling directly into her web.
Sound and light don’t travel as well in water as they do on land. Fish, therefore, need pheromones to communicate. The Caribbean Bluehead Wrass Fish lives in a harem. The largest Wrass in the group is male, and he exudes chemicals that prevent the other fish from developing male gonads. He lords over his females until he gets old or killed, and then the pheromones go away. Now the largest female in the harem becomes male, makes new pheromones of “his” own, and mates with his former electric-blue comrades.
As we move up the evolutionary tree, a special organ designed to detect these powerful chemicals appears. It is called the vomeronasal organ, or VNO. The VNO responds to chemicals in the environment by transmitting nerve signals directly to the brain. Most animals that evolved from fish use the VNO to detect pheromones, but in humans it breaks down. For us, the VNO is the neurological equivalent of the appendix. It simply doesn’t work anymore. The human VNO is small and mucousy and so difficult to see that scientists have just recently discovered that everybody has one. It lies dead between our mouth and our nose and it looks like two tiny, parallel tubes of flesh. Upon close inspection of human cadavers, researchers have found that it lacks the nerves it needs to function in our bodies. But this vestige made our ancestors fight and mate, simply because a nearby molecule drifted inside and sent nerve impulses to the brain. Most of our living relatives still use this organ, and scientists have begun to study how VNO stimulation can change animal behavior. From single-celled animals that came together according to chemicals in the ether to eyebrow-raising, art-appreciating humans, we can tell a new story about our evolution by examining this teeny, spongy footprint to our sensual past.