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
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.
the ways in which "gene toxins" attack DNA
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.
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.
act as "genotoxins." That is, they react with DNA, causing it to
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
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
a cancer-causing ingredient in barbeque affects researcher's eating
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.
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.
student manages family and professional lives
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.
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.
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.
plays a key role in scientific research
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.
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."
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.
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
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.
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.
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
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."
Stone's home page
of Science, Engineering and Technology Program