The tiny crystals are beautiful. Green, blue, purple and other colors blend to make pictures worthy of the Museum of Modern Art. Jennifer Swift, assistant professor of chemistry, thinks about crystals all the time.
For the nonscientist, crystals may conjure up fifth-grade science experiments or “healing” quartz necklaces. Yet crystals exist in a much wider variety of environments than most people realize. They also come in vastly different shapes and sizes. Swift says that crystals may be loosely categorized as either “good” or “bad” – a designation largely determined by what the crystals are made of, where they grow, and sometimes their shape and perfection.
Bad crystals, Swift explains, include cholesterol crystals, which are the building blocks of gallstones and are found in arterial plaques, and uric acid crystals, which are a constituent of some kidney stones and are responsible for gout. Swift and her team of graduate and undergraduate students are researching how these crystals grow so they can devise ways to prevent them from forming.
In contrast, she notes, “good” crystals are manipulated to create medications that can be pressed into tablets and taken orally. When crystals used in drug development grow in the form that pharmaceutical companies would like them to, tablets are stable enough to last on the shelf and soluble enough to dissolve when you ingest them. If the crystals grow in the “wrong” form, the active ingredient may be totally insoluble or the drug crystals might not be stable enough to have a reasonably long shelf life. It can mean the difference between medications that may be taken orally versus those that must be injected into the patient. As one might guess, drug companies, doctors and patients prefer the former.
Polymorphism, or the ability of a molecule to exist in more than one crystal structure, is a serious concern for pharmaceutical companies.
“You can patent a molecule, and you can patent a crystal,” notes Swift, who came to Georgetown in 1999. “Companies go though a lot of trouble making sure they patent the drugs they want to develop. If they go through the whole development process and suddenly find that a different crystal form appears, then they’re not manufacturing the same thing. Important drugs have been pulled off the market because of this.”
Among funding sources for her work are the National Science Foundation (NSF) and the American Chemical Society. She also has received support from the Clare Booth Luce Program, which provides significant private funding for women in science.
Richard Bates, chair of the chemistry department, calls the research in Swift’s lab “exceptional because of the comprehensive nature of her studies and data of exceptional quality.” And Bruce Foxman, a professor of chemistry at Brandeis University, says Swift’s “studies on the growth of uric acid and cholesterol crystals, coupled with the knowledge of crystal nucleation, will very likely lead to clinical methodology for preventing gout and/or other uric acid-related diseases or conditions.”
Clinical applications of this work could come about in 10 years, 20 years or never. And there are many scientists working to find solutions for these medical problems.
“As with most diseases, there probably is not one root cause for how it starts,” Swift explains. “The best anyone can do is try to understand the basics of how these processes work. It’s the same with all diseases – no single study provides the magic bullet, researchers are only able to tackle small pieces of the problem at a given time.”
Because kidney stones or gallstones are generally neither life-threatening nor daily recurrent ailments, Swift says the research doesn’t receive the same amount of attention from the pharmaceutical community as research on cancer or AIDS, she says.
“However, anyone who has [these conditions] understands firsthand the importance of studying them,” Swift says, and smiles. The professor’s grandmother, mother and sister had their gallbladders surgically removed before the age of 40. Swift wonders if she might be next; she turns 36 in July. “I may only have four years until people begin to question my motivation for this research,” she jokes.
The personal connection is really a coincidence – she’s been working with crystals since she started pursuing her Ph.D. at Yale. She also worked with crystals as a postdoctoral researcher at the University of Minnesota.
Michael McBride was Swift’s advisor at Yale. “[At scientific meetings] I have glowed with pride to hear her present the results of her work and to know that I played some role in allowing her to follow her star,” says McBride, Yale’s Richard M. Colgate Professor of Organic Chemistry. “Her most recent work on uric acid crystallization is of particular interest to me, because I have suffered from kidney stones. In fact, when she came to interview at Yale before graduate school, I had an attack while she was in my office. I have high hopes that her work will help me avoid such events in the future.”
He also says Swift’s original research on completely different crystal materials in his lab “proved so useful that we are still studying them in my laboratory almost 15 years later… without Jen to lead the way, we would never have gotten launched into this line of research.”
Swift has been recognized nationally for her work. She received the 2005 Margaret C. Etter Early Career Award from the American Crystallographic Association, and last year was one of only 13 chemistry professors nationwide to receive a prestigious Camille Dreyfus Teacher-Scholar Award.
But Swift likes to point out that most research, including hers, is a team enterprise.
“The actual science is fascinating, challenging and societally relevant, but I honestly look at my success here as being defined not only by the particulars of the research per se, but rather by the accomplishments of the people I’ve trained,” Swift explains. “It’s my students I’m most proud of. I can come up with clever and creative projects, but without good people to work on them, then the research simply doesn’t move forward.” She typically has about five graduate and five undergraduate students working in her lab.
Former student Ryan Sours (G’05), now a postdoctoral research associate in the chemistry department at the University of Washington, notes that the Swift lab was the first to use atomic force microscopy (AFM) methods to study how the molecular building blocks of kidney stones and gallstones grow. The AFM works by scanning a tip across a crystal sample to trace out a topographical map, Swift explains. But this type of topographical map has the resolution that allows researchers to see individual molecules. This makes it possible to take numerous measurements over time and create images so Swift and her team can observe the way a crystal is growing on a molecular level in actual time.
The team already has determined the rate of growth at the molecular level for pure uric acid using the lab’s AFM, Sours says, and there also has been some success at inhibiting crystal growth using a particular dye.
“Using the Atomic Force Microscope, we can actually image structures on the surface that are the height of one molecule of cholesterol, which is beyond the capabilities of a typical high-power laboratory microscope,” Richard Abendan (G’05) says. “We can actually see surfaces changing, essentially visualizing how individual molecules of cholesterol add or leave the crystal. This is exciting, since now that we have a better understanding of the cholesterol surface in a molecular level, we can lay the groundwork for future work.”
Swift’s personal style in the lab is much admired among her students.
“We have a lot of scientific freedom in the lab, where we can go on tangents on our own and come up with solutions of unexpected scientific problems along the way, which is good training for any Ph.D. scientist,” says Abendan, who works with cholesterol crystals. “She also has us write drafts of our papers, which trains not only the scientist but the presenter and writer in us.”
Swift is well-published, and all of her papers list undergraduate or graduate student authors first. Abendan says she also puts “a lot of energy” into helping students improve the quality of their research talks and posters they present nationally and internationally.
The professor is quick to praise her students for their work and the many presentation awards they have received at conferences, but is considerably more reserved in speaking about her own accolades. Sours characterizes her as “very modest,” a phrase repeated by some of her other students.
“I think the results of her efforts not only improve the reputation of our lab and research, but I think it also reflects well on Georgetown,” he says.
Catherine Ford (C’05) started working in Swift’s lab in her sophomore year.
“I decided to work in the lab based on what I had heard from undergraduate students already working there,” she says. “Jen is someone who is very easy to work for. Her door is always open for any questions, and she is always in and out of the lab talking to one person or another.”
Ford worked on a project involving uric acid and a natural dye called uricine. “Uricine is a dye that is found in kidney stones,” explains Ford, who plans to do service work after graduation and then apply to medical school. “Through an extraction process, I have isolated uricine from uric acid kidney stones. We then looked at how this dye – when incorporated into the crystal structure of uric acid grown in the lab – changes the shape of these crystals.”
Ford says she really enjoys working in the lab.
“Everyone in the lab gets along very well,” Ford says. “Both the undergraduates and the graduate students work side by side and we have all become friends.”
Swift makes efforts to encourage camaraderie in the lab. “I believe that students are more productive when they are working in a supportive collegial environment and know that their opinions and efforts are valued, ” Swift says. She always remembers to bring in birthday cakes for students’ birthdays and has entertained the group at her home many times. Her current research team also includes Rupa Hiremath (G’06), Amanuel Zellelow (G’05), Megan Carroll (C’06), Joseph Basile (C’06), Caitlin Fogarty (C’06) and Kun-Hae Kim (C’07).
Steve Varney (C’04) says doing research as an undergraduate exposed him to the “actual world of working in science.” Now a researcher for the Weinberg Group in Washington, D.C., Varney says his work these days relates more to health than chemistry, but that there are “many basic principles I still use that I learned in Jen’s lab.” At Georgetown, Varney researched the creation of surfaces known as “self-assembling monolayers,” which work especially well for crystals that are difficult to grow and might be useful for pharmaceuticals.
“While working for Jen, I was exposed to the practical side of science,” he says. “Not only observing or reading from a textbook what goes on in a research lab, but doing research myself.”
Dorothy Fink (SNHS ’03, M’07), who worked with Swift for three years, is now at Georgetown’s School of Medicine and hopes to become a pediatric oncologist.
“Despite Jen being incredibly busy with the many graduate students in our lab, writing grants, teaching and numerous other responsibilities, she remained tireless and was never too busy to assist the undergraduate students,” Fink says.
“One of the best parts of being here at Georgetown for medical school is that Jen continues to be an inspiration and role model to me,” she adds. “Jen challenged me and encouraged me to understand mechanisms that occur in our bodies, and this led me to be interested in the aberrant growth that occurs in cancer.”
When teaching her organic chemistry courses, Swift takes time to show undergraduates how to organize information and make the right connections between learned concepts.
“In most lower-level science courses, facts are given out in discreet units,” she notes. “But organic chemistry knowledge builds on what is being taught. Students who take a foreign language are expected to understand many words and are graded on their ability to put them together in coherent ways. Asking a student to assemble the correct reagents and reaction conditions to make and characterize a synthetic product is just the same.”
Swift knows that learning the science is hard work, though, so she created a free, peer-tutoring program for students enrolled in general and organic chemistry courses.
“Sometimes students are more comfortable asking peer tutors to explain concepts rather than going straight to the professor,” Swift says. “The tutors also benefit and find that serving in this capacity is a very valuable experience.”
In 2004, she also redesigned the format of the Organic Chemistry II course so that a series of conceptually related experiments would be performed over several weeks instead of the more traditional approach in which isolated experiments are conducted each week. Her course development work was supported through a “Teaching, Learning & Technology Fellowship” awarded by Georgetown’s Center for New Designs in Learning and Scholarship as well as an education grant from NSF.
College Dean Jane McAuliffe says Swift “characterizes what is special about the sciences.”
“She moves seamlessly between her teaching and research and serves as an important role model and mentor to both her undergraduate and graduate students, encouraging them to explore and to consider the impact of their work.”
Chemistry chair Richard Bates says “Jen has proven to be an exceptional innovator in undergraduate teaching at Georgetown.”
The combination of solid coursework and time in the lab is a winning one, says Swift’s students.
“Research has done a few things that were very helpful for me,” Ford says. “Initially it made me a lot more comfortable and confident in lab settings, which I transferred over to my lab classes. … I think research is important for undergraduates because it gives people a chance to work on the their own project, which will promote independent thinking and decision making.”
The beauty of the crystals continues to fascinate both professor and students. When asked which crystals she finds most attractive, Swift says, “I don’t have a favorite. It’s like asking which kid a parent likes best.”
