Bonding through Biology

Even before they formally start college classes, sixteen freshmen learn the rudiments of research in a Duke science lab.

Project WILD, Duke’s oldest pre-orientation program, has a well-honed gear list. The list goes out to the not-quite-yet freshmen who sign on for two weeks of hiking in western North Carolina: broken-in hiking boots, waterproof rain jacket, flashlight, medical-insurance card, and so on.

Project Search (whose partakers prefer the snappier “pSearch”), Duke’s newest pre-orientation program, hinges on moving liquids gingerly through pipettes rather than moving students purposefully along mountain trails. Every day for two weeks, beginning in mid-August, the sixteen pSearchers, evenly split between men and women, spent up to six hours in a lab in the sub basement of the Biological Sciences Building. They were chosen—by a team of older students who work with the program—through an application process that included two essays. In one they wrote about a professor whose particular research they’re drawn to; in the other, about why they’re interested in research in general.”

The question of whether Duke should invest in this particular early exposure to research was first formulated by two students. Alex Robel and Anthony Lee, 2010 graduates and A.B. Duke Scholars, started talking about a pre-orientation research program in the summer of 2008, while they were in Ecuador through the scholarship’s service-learning project. That fall, they distributed a survey to gauge why freshmen might not pursue research. They identified as key factors a lack of earlier research experience, poor communication with the faculty, uncertainty about whether a research trajectory would be right for them, and an inability to find a position in a lab.

Those targeted by pSearch have a rough interest in research but have never put that interest to the test. “While all Duke students excelled in high school, obviously not all high schools are equal,” Lee says. In 2009, he helped recruit a pSearch pilot group that had students with “great A.P. science scores,” he says, “but some never did a ‘wet’ lab in high school—all their labs were virtual.”

In harmony: With one ear (each) tuned to musical accompaniment, Justin Kotliar and Stephanie Downey record findings. Megan Morr

As they sample science in the non-virtual world, this year’s students are trying to create “proteins of interest” from DNA samples, largely from mice and fruit flies, donated by Duke labs. Those labs plan to make experimental use of the newly synthesized proteins. Every cell contains thousands of different proteins, which together play a big role in cell function. The students “are not doing a purely academic exercise,” says Eric Spana, assistant research professor of biology and the program’s lab adviser. “They’re building something that researchers want, and students understand the science better when it really matters.”

Early on, the pSearchers learn about transcription and translation: Cells use the two-step process to read each gene and produce the string of amino acids that make up a protein. “The central dogma of biology tells us that all proteins are derived from a specific sequence of RNA, and that that RNA is derived from a specific sequence of DNA,” Spana explains to a visitor.

One of the tasks for the students is to amplify the DNA using a technique called PCR (polymerase chain reaction) and clone it into E. coli bacteria. E. coli can be stimulated to transcribe the gene into RNA, and from there to translate it into protein. They’re particularly useful for genetic experiments because they grow rapidly, at a rate of one generation every twenty minutes under typical growth conditions.

From that point, the students will purify and extract the protein from the bacterial cells. The end product—ideally—is a solution containing the protein requested by each of the faculty researchers. “We are not trying to push students into doing research, but simply to let them make the best-possible educated decision about their own course,” says cofounder Robel, who adds that nearly all of the ten pSearch participants in the 2009 pilot program sought placement in a lab. A double major in earth and ocean sciences and physics, with a minor in mathematics, he did research on climate and physical oceanography, as well as writing senior theses in both of his majors. He’s now in Harvard University’s Ph.D. program in earth and planetary sciences.

Lee, the other pSearch cofounder, says students may understand the character of a research university, but they don’t necessarily appreciate their own potential for participation. Many of his friends didn’t get to taste research until late in their college careers, he says. “It wasn’t because they weren’t talented or proactive. It was because Duke had so much to offer that laboratory research was often postponed for the next semester, or the next, or the one after that.”

A biology major as an undergraduate, Lee spent all four years and portions of every summer doing research at the medical center—first working on a fungal pathogen, then on astrocytes, the most abundant cell type in the brain. Astrocytes’ exact role has long been a mystery. His lab mentors “really encouraged me to ask interesting questions,” he says, and they treated him not “as a lowly undergrad” but rather as a colleague who was expected to “play substantive roles in the lab.” He thought more and more about pursuing physician-scientist training; he’s now in the M.D./Ph.D. program at the University of California-San Francisco.

On a typical morning, today’s pSearchers are doing what they’ve been doing a lot in the course of the program—watchful waiting. They’re looking over instructions on the lab whiteboard: “Suspend pellet in 10 ml 3-PER by vortexing/pipetting up/down”; “Gently shake homogenous mixture for 10 min.”; “Centrifuge @ 15,000 rpm for 15 min.”; “Add 2 x 3 ml elution buffer and collect fractions.”

Reviewing the remains of the day: clockwise from left, Cameron McKay, Joy Liu, Lindsay Gaskings, Kristie Yang, and lab adviser Eric Spana. Megan Morr

During the slow stretches, several are exercising their iPhones. They’re tuned into the Internet-music site Pandora— appropriately, the product of something called the “Music Genome Project”—which provides an endless stream of songs that supposedly follow a particular listener’s criteria. (Pop-rock/folk/acoustic seems to define the group preference.) One student, who puts herself into a spin in her lab chair, jokes that she’s mimicking a centrifuge. Another is crafting a hand puppet from her rubber glove. A few speculate on the whereabouts of the lab’s unofficial mascot, a black-and-white rubber orca whale, which tends to get tossed around in not-so-gentle fashion.

pSearcher Josh Weiss makes an easy shift in conversation theme from science to his cello playing. Weiss took A.P. courses through high school in biology, chemistry, and physics. He also worked on a genetics-related bioinformatics project at Long Island’s Cold Spring Harbor Laboratory. “But none of that was in a wet-lab setting,” he notes. Observing how tightknit the pSearchers have become—through such shared activities as indulging in cardio-dancing, joining the crowd for a Durham Bulls game, visiting the local Target for critical supplies like pita chips, and watching a meteor shower through Duke’s teaching telescope—he offers a visitor a “geeky science quote”: “We’ve formed strong chemical bonds and become a polymer of awesomeness.”

On the other side of the lab, Kristie Yang, whose last exposure to biology was in her freshman year of high school, adds, “There’s no real stress here. We’re just here to learn. And I like to see the implication of what it is that I’m learning. It’s not like the standard high-school biology lab, where you dissect a frog, you finish the assignment, and that’s the end of it.”

Outside the lab, the pSearchers meet for lunch with a Duke researcher almost every day of the program; they get a taste of a research repertoire including the nanotechnology of harvesting atoms to grow copper wires and the science of injecting proteins that target tumors. One of those gatherings features Steve Nowicki, dean of undergraduate education and a professor in the departments of biology, psychology, and neurobiology. He sketches his trajectory from a budding classical musician to a student in a college biology course that “changed my life” to a scientist whose lab looks at the function, perception, and evolution of complex bird songs. Understanding how birds communicate brings us closer to understanding what makes us human, he says. He says he’s drawn to scientific questions that are complicated but that, through technical skills and free-floating imagination, seem answerable.

Nowicki proceeds to test the skills and imaginations of the pSearchers, asking them to think up particular experiments— entailing everything from brain scans to the strategic positioning of loudspeakers—that would address particular research problems in his field. “Science is a lot like carpentry,” he says. “You use the simplest tool to get the job done.”

In a later science-themed lunch, over salad and lasagna, the students hear from Nancy Andrews, dean of the School of Medicine, whose lab contributed DNA for the pSearch project. Among her lab’s interests is hemochromatosis. Individuals who suffer from the disorder have trouble absorbing iron from their daily diet. Andrews tells the students she was drawn to work that would satisfy both an intellectual curiosity and an interest in making a clinical contribution. Even before she winds down her presentation, the students are posing questions: How are diseases related to excess iron diagnosed? Why is bloodletting, with its old-fashioned connotations, still considered an effective treatment when we have such a powerful array of pharmaceuticals? Is it reasonable to contemplate a cure for hemochromatosis? Can the genes underlying such diseases be carried by individuals unknowingly? Are there tests to determine if someone is a carrier? Are different ethnic groups variably affected?

Summing up the guest speakers, one student observes, “They remind you how much you still have to learn. I get maybe 50 percent of what they’re talking about.”
In their lab, pSearch’s community of learners is spurred by four student codirectors, two of whom, Chris Clayton ’13 and Stephanie Dudzinski ’13, are veterans of the inaugural pSearch. Clayton took A.P. chemistry and physics but not A.P. biology in high school. He says his parents originally encouraged him to pursue Project WILD among the pre orientation offerings. After all, college life would offer plenty of academic enrichment.

But Clayton—who has since joined the Outing Club to satisfy his adventurous interests—considered pSearch “too good an opportunity to pass up.” Later he got an instantly positive response from his first-choice lab, run by assistant research professor of biology Nina Sherwood Ph.D. ’98, who is interested in a host of proteins and their role in cellular growth and transport.

There’s a lot of “basic stuff that’s actually critical” in terms of lab techniques—mastery of automated pipetting and sensitivity to avoiding contamination, for example—that carries over from his pSearch days. A premed student with an interest in global health, Clayton says he keeps balance in his life through his ukulele playing, which becomes a feature of the nightly pSearch meetings that look back on the work of the day.

“It sounds cheesy,” says Dudzinski, “but pSearch changed my life at Duke.” In high school, she took A.P. courses in math, physics, chemistry, and biology, but she never had a lab experience. Before enrolling, she had acquainted herself with the work of some Duke researchers, but she says she was skeptical that a freshman could secure work in a lab. (She’s since discovered that some labs seek out students with four years to offer.) Her newfound confidence has propelled Dudzinski, a biomedical engineering major, a considerable distance—even before she proceeds on her life plan to pursue a joint M.D./Ph.D., become a neuro-radiologist, and “conduct research in using nanoparticles to enhance medical imaging techniques.” At the Pratt School, she mentors younger students through the Society of Women Engineers.

Dudzinksi started last year in the lab of biomedical engineering professor Tuan Vo-Dinh, which she describes as “a nanobiotechnology lab.” This summer, she worked there as a Howard Hughes research fellow. (Vo-Dinh, director of the Fitzpatrick Institute for Photonics, has published more than 330 peer-reviewed papers.) Her research blog is sprinkled with expressions of unfettered enthusiasm and scientific seasoning alike: “When functionalizing my nanoparticles with the cell-penetrating peptide TAT in the morning, it was easy, breezy, and beautiful.”

Easy and breezy may not always characterize the lab routine, but “there’s nothing more exciting than asking a question and discovering the answer,” longtime biology lecturer Ron Grunwald tells the students. The program’s last speaker, Grunwald ’80 became director of the Undergraduate Research Support Office and associate dean of Trinity College this summer. (He began his Duke experience with that well-established pre-orientation program, Project WILD, an experience that he recounts with vivid recollections of hauling around canned mackerel.) Research, he says, should be part of a college education and not merely ancillary to it. “What you do in the laboratory will inform what you do in the classroom. What you do in the classroom will inform what you do in the laboratory.”

Grunwald talks about science as a social activity. After all, it hinges on connections among colleagues, or on peer reviewing, more than on solitary doings. The wellbonded pSearchers can identify with that statement. They can also identify with Grunwald’s added point, that research brings frustrations: They had to devote an extra day in pursuit of the results they were after. Even a failed experiment can stimulate a new hypothesis and lead the research down a new avenue of investigation, Grunwald says. Referring to the value of the novice scientist’s latching onto a mentor-scientist, he offers the students what he calls basic Talmudic advice: “Be ambitious and take the initiative. And go find yourself a teacher.”

Afterward, he’s encircled by pSearchers. Their first college classes are more than a week away, but they’ve mastered some early lessons.

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