Plumbing the secrets of the Stone lab

By Renae Virata / Intern
September 17, 2001

It was an unusually warm fall day when I began my research laboratory internship with Michael Stone, an associate professor of chemistry at Vanderbilt University. His lab happened to be directly below the general chemistry labs where I had, quite unimpressively, performed a dozen canned experiments years before. Recollection of my previous laboratory experience reinforced my nervousness, so I held my head high and took a deep breath to ready myself before entering the inner sanctum of real research.

For most undergraduates, the chemistry lab is a confusing place with a stuffy, intimidating environment. The introductory classes do not reflect the true essence of scientific research. I didn't realize it at the time, but, by walking down those steps to the floor below, I became one of the privileged few who can appreciate the gap between the classroom labs we always dreaded and the working research labs below we never knew existed.

The internship that brought me to the Stone lab is part of the Communication of Science, Engineering and Technology major in Vanderbilt's College of Arts and Science. The major was established to help bridge the gap between the science world and the lay public. Through interaction with scientists and students in a working research lab, my job as an intern was to study the way that actual research is conducted.

When I walked into Stone's office for our first meeting, I noticed that his desk was piled high with grant proposals, tests to be graded and other documents needing his attention. He seemed to embody the busy scientist who had little time to worry about the angst of an undergraduate. As we talked about the upcoming semester, however, his concern and genuine interest in my experience put me at ease.

Investigating the ways in which "gene toxins" attack DNA

Stone began working at Vanderbilt as a beginning researcher 17 years ago. He was hired to maintain Vanderbilt's first high-field nuclear magnetic resonance spectrometer, an instrument that is central to his own research. One aspect of his studies concerns the effects that the fungal toxin, aflatoxin B1, have on the structure of DNA and, in turn, how these effects change the way in which the genetic information encoded on DNA is expressed. Close partners in his research are Thomas M. Harris, Centennial Professor of Chemistry, and his wife, Associate Professor of Chemistry Constance M. Harris. Their laboratory synthesizes chemical compounds, called oligonucleotides , used in Dr. Stone's work.

In addition to aflatoxin, researchers in his lab also study the effects that a number of different toxic chemicals have on DNA . These include: the polycyclic aromatic hydrocarbons found in charred meat and automobile exhaust; malondialdehyde produced by the decomposition of fatty substances in the body; and, butadiene and styrene, feedstocks used in large quantities by the plastics and rubber industries.

These substances act as "genotoxins." That is, they react with DNA, causing it to mutate and so damaging the genetic information that it carries. This information gives us our eye color and a number of other basic physical characteristics, as well as determining our susceptibility to a broad range of diseases. Exposure of fetuses to genotoxins that target genes involved in development can lead to spontaneous abortions or birth defects. In adults, signals sent by damaged DNA sequences can induce tumor growth.

The interest of Stone and his colleagues is concentrated on areas in the genome where mutations appear to be especially deleterious. One of these areas is the Ras-61 oncogene . Other examples are the protooncogene and tumor-suppressor gene sequences that also may be associated with increased incidence of human cancer.

Studying a cancer-causing ingredient in barbeque affects researcher's eating habits

The research that the scientists in the lab perform can have an impact on outside lives. For example, Hye-Young Kim, a post-doctoral scientist, has been studying a family of chemicals called polycyclic aromatic hydrocarbons (PAH) found in charred barbecue scraps, among a number of other sources. Laboratory animals, when fed large amounts of the burned parts of charbroiled foods, have exhibited an increased risk for certain types of cancer. Kim explained how her study of PAH has changed her daily eating habits: "Now, I slice off the burned parts even though I know such a small quantity is harmless...even though they're the tastiest parts," she smiled.

Others in the lab saw the implications that their research could have on future cancer victims. Chemistry graduate student Keith Merritt was working with DNA damage caused by a chemical found in cigarette smoke and rubber factory emissions. He appreciated the fact that his research is contributing to the giant "umbrella" of cancer research being conducted around the nation and the world.

"One day, we could possibly develop medicines stemming from this research not just to treat cancer but also to prevent the initiation of cancer by these genotoxins in the first place," Merritt said.

Working with students and researchers like Hye-Young and Keith, I felt my limited view of scientists expand. They were people whose work affected them personally as well as professionally.

Post-doctoral student manages family and professional lives

Nathalie Schnetz-Boutaud, the post-doctoral student who supervised me, completely erased my past notions about the singular nature of scientists and their research. Running between picking up her children from daycare, mentoring students like me in the lab and doing her own studies on the DNA damage induced by malondialdehyde, Nathalie demonstrated that life as a professional scientist and a mother was hectic but manageable. The first time we met, she surprised me with her denim overalls, charming French accent and sprightly disposition. She added another dimension to my growing perspective of a research laboratory, one that the intimidating setting of my past lab experiences had not provided. Consequently, I found it easier to interact on personal as well as professional levels with the researchers.

As I became more familiar with the Stone laboratory, I realized that the word which best characterizes it is variety. There was a wide variety in the research: Every scientist had a unique focus for his or her study. The people themselves were very diverse and came from different parts of the world. Students hailed from as close as Chattanooga to as far away as California. Post-docs came from all over the world: India, Switzerland, Korea, France and China.

Each scientist had a different story to tell about his or her experience in coming to the lab. When we had a few moments away from the lab, Markus Voehler, an NMR spectroscopist, readily told me about his native Switzerland. He said that the decision to leave his homeland and move to the United States was difficult to make. After eight years in Nashville and Vanderbilt, however, Voehler said that he has never regretted his decision.

Researcher Tandy Scholdberg-who proudly calls Leavenworth, Kansas home-provided me with another aspect of the lab: the graduate student experience. Between cramming for tests and conducting research on DNA damage caused by an epoxide of styrene, she managed to balance her responsibilities as both a student and a researcher. She answered many of my most pressing science questions and at times had a few of her own for Schnetz-Boutaud. She and Merritt studied for midterms and finals together, conferring every so often about their research-with a few personal conversations thrown in here and there.

Networking plays a key role in scientific research

Such networking is an important part of scientific research. It also contributes to the overall camaraderie in the lab and Stone emphasized that he actively tries to promote it. "Communication is key to the laboratory experience," he said. Although engaged most often with logistics (grant proposals, meeting schedules, etc.), he encouraged everyone to communicate with him and with each other. He held weekly meetings to provide the researchers with an opportunity to collaborate on ideas and findings. The meetings also gave Stone the chance to catch up on the researchers' work and just to chat.

Another attitude that Stone promotes actually stems from his upbringing. His father and godfather are musicians. Others in his family, including a grandmother, grandfather and several uncles, were artistically talented. They imbued in him an appreciation for creativity and art that Stone encourages in his lab. "A certain amount of creativity is necessary to be able to think a step ahead in research," he explained. "As a researcher, you are looking for something that exists but is unknown...to be able to imagine it is an integral step in making a discovery."

The ability to imagine and create is reflected in the three-dimensional DNA images that the team generates to study the structural discrepancies that their respective genotoxins cause. They make use of the instrument that brought Stone to Vanderbilt-the nuclear magnetic resonance (NMR) spectrometer. The two-story machine, housed in its own room in Stevenson Center, is the center of a small complex where scientists control its operation and record the data that it produces.

Laboratory resembles a science fiction movie set

The room reminded me of a movie set for a science fiction thriller: Scientists busily working with revolving images on giant computer screens in one room looking onto another that holds the giant NMR machine in all its glory, like some top-secret instrument being used for clandestine research.

The NMR spectrometer may not be top secret, but it is amazing. It uses a powerful, superconducting magnet and ultra-sensitive probes and antennae to reveal some of the most closely held details about the structure of complex biological molecules, such as DNA. To do so, all it needs is a tiny sample of DNA, usually only one-half of a milliliter in volume. It is a mere pinch when compared to the tremendous bulk of the machine itself.

The spectrometer produces special spectra that the researchers analyze to determine the nucleotide sequence of different segments of DNA. The sequence information can then be used to generate the DNA structures that the researchers use to identify the structural discrepancies caused by the genotoxins. In this fashion, they are gaining new insights into the correlation of the changes in the DNA structure and the initiation stages of cancer. "If we understand the causes of cancer, we will have a better shot of curing it," Stone explained.

Bridging the ultimate goal of the research lab with the personal and professional contributions of each researcher provided a clearer picture of how an actual lab runs. The faces of the men and women who contribute to the science that shapes our daily lives in the fields of medicine, technology, and research were no longer invisible in my eyes. As I worked with the members of the Stone lab, shadowing them in their endeavors and sharing in their trials and triumphs, my image of scientists took a more realistic and personable and much less daunting shape.

Stone summed up a particularly important lesson during one of our last interviews: "All of us, even if we aren't professional scientists, are called upon to make scientific decisions or evaluate data that we come across in our lives. From time to time, we all need to think like scientists. So science is pretty important for everyone."

Prof. Michael Stone's home page
http://www.vanderbilt.edu/AnS/Chemistry/chemmain/stone.html

Communication of Science, Engineering and Technology Program
http://www.vanderbilt.edu/News/srcomm/