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” attach 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
oligonucleotides1, 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 DNA2. 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.
1
Molecules that contain small numbers of nucleotide units.
There are four nucleotide bases that make up the two-stranded double helical structure of DNA: adenine,
guanine, cytosine, and thymine. Adenine pairs with thymine, and guanine pairs with cytosine. Each member
of a pair is bonded to the other from opposite strands.
2
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Plumbing the secrets of the Stone lab
These substances act as “genotoxins.” That is, they react with DNA, causing it to mutate3 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 oncogene4.
Other examples are the protooncogene5 and tumor-suppressor gene6 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 7
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
3
A mutation occurs when the correct nucleotide bases, the basic chemical units in DNA, are replaced with
incorrect ones.
4 A gene associated with the initiation of cancerous growth.
5 A normal gene, usually concerned with the regulation of cell proliferation, that can be converted into a
cancer-promoting oncogene by mutation.
6 A gene whose normal function is to suppress tumor formation. Certain cancers have been associated with
mutations of tumor-suppressor genes.
7 An epoxide of 1,3-butadiene. (See next footnote for definition of epoxide.)
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Plumbing the secrets of the Stone lab
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 8 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 pays 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.9
8
An epoxide is any compound that contains an epoxy group (an oxygen atom directly attached to two
carbon atoms) attached to two carbon atoms.
9 The spectrometer makes use of a phenomenon known as nuclear magnetic resonance, or NMR, for which
the instrument is named. The sample, like everything in the universe, is composed of atoms. It so happens
that the nuclei of certain atoms, including hydrogen, carbon-13, and phosphorous-31, act like tiny magnets.
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Plumbing the secrets of the Stone lab
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."

When placed into the spectrometer, a sample is exposed to a powerful magnetic field. The nuclei tend to line
up in the same direction as the field. Then the sample is exposed to an intense pulse of radio waves. This
pulse contains frequencies that match those that the magnetic nuclei can absorb. Following the pulse, most
of the nuclei re-emit the energy that they absorbed in a process called relaxation. The NMR probe, which
produced the pulse, also acts as an antenna that detects these emissions. Because the energy that an
individual nucleus in a molecule emits is affected by its relationship with the other atoms in its immediate
vicinity, analyzing the spectrum of these emissions allows the scientists to determine the structures of
complex organic molecules like DNA.
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