By Allison Byrum
Dec. 1, 2000
all wear glasses and white coats. Everyone knows that. The labs
are small dark rooms filled with funny-shaped glassware and colored
concoctions that bubble and smoke. Everyone knows that scientists
are generally men with no families who sleep on cots in the corner
of the lab beside the freezers and incubators.
Of course, they
are incomprehensibly brilliant and have always been so: childhood
prodigies who had toy microscopes instead of toy trucks and went
to after-school biology enrichment programs at the local college
during grade school before finally enrolling in college at the age
that research is predictable. Every day a new breakthrough is made
and a drug technique is discovered that will most certainly change
the world tomorrow. On the days that there isn't a breakthrough,
it's simply because there's nothing new to discover. It's all been
Unless you are
a scientist or are familiar with science, you cannot appreciate
just how shocked I was when my "stereotypes" and I actually began
working in a research lab. I say we both began working, but in reality
I worked, my preconceptions and prejudices did more of a disappearing
For two months
I fumbled around Dr. Ann Richmond's lab in the Cancer Biology department
of Vanderbilt's Medical Center North. It was an amazing experience.
Richmond's lab is currently researching MGSA, or Melanoma Growth
Stimulatory Activity. MGSA is a protein involved in tumor growth
in melanoma, the most serious form of skin cancer that is responsible
for approximately 7,700 deaths a year. MGSA however, is not limited
to melanoma. Since its characterization, it has been found in breast,
lung, and other cancers as well.
in characterizing MGSA is the late 1980's. Though accompanied by
both strong critics and strong competition, the search for MGSA
was far more successful than Richmond originally hoped. The initial
investigation of MGSA, along with research on other proteins like
it, opened the floodgates to a new family of proteins called chemokines
that have since been linked to biological processes including wound
healing, tumor growth, and chronic inflammation. MGSA is a chemokine
and is found in all animals.
MGSA is a key
to wound healing. When our bodies are injured-a cut on an arm or
a blistering sunburn, for example-the cells near the wound send
out SOS signals to the surrounding tissues, much like an emergency
response beacon on a downed aircraft sends out the message that
"we've been hurt; we're here; come help us!" Cells, however, use
a chemical messenger, MGSA, that travels into the cells around the
wound and calls out the body's "rescue team": infection fighting
white blood cells, new skin cells, and new blood vessels. Once this
team is assembled at the site of the injury the SOS message is cut
off. Help has arrived and no more MGSA is dispatched.
when the production of MGSA does not stop when it should. The stream
of white blood cells, new skin cells and blood vessels continues
to arrive even when they are not needed. The result is a massing
of cells called a tumor that is being fed by our own bodies.
her colleagues are investigating what turns off the production of
MGSA and why in some cases production continues when it should stop.
One can imagine a breakthrough leading to the discovery of an MGSA
inhibitor that could be injected into a patient with a tumor and
stop the tumor from growing. But that's not how science usually
works. Breakthroughs are rare and when they do come, it is often
not in the way the scientists would have guessed. Science is a step-by-step
process driven by different kinds of people investigating different
sides of one problem: how does the universe and everything in it
misconceptions begin dissolving
views about how science works was just one of a number of misconceptions
that began to dissolve the moment I stepped into the Richmond lab.
Richmond's team is made up of six post-doctoral fellows ,
two laboratory technicians with bachelor's degrees in science, one
of whom is working on her master's degree, and a lab manager with
a master's in veterinary science and sixteen years of scientific
experience. Finally, there are two graduate students, one working
toward his Ph.D., and the other in a MD/Ph.D. program. None of them
fit my expectations.
is the lab technician who supervised me. The antithesis of my image
of a scientist, Yu is a small woman in her early thirties who came
to the United States about four years ago. She met and married another
Chinese native in 1997 here in the United States. While Yu is earning
her master's in biology, her husband works with Internet technology.
She is not male, not single, and did not graduate from college when
she was fourteen.
Not even the
lab matched my preconceptions. In stark contrast to the small dark
laboratory of my imagination, Richmond's lab consists of two large
rooms with long continuous workbenches running down the center of
the room and pieces of equipment lining the walls. Another smaller
room serves as the office, housing several computers and a microscope.
The labs are colorful and clean. Black bench tops are contrasted
with sparkling clean glassware and colorful labels. There were no
bubbling solutions or dusty corners. I could not find a spider web
anywhere! Clearly, research was not going to be exactly what I had
First of all,
there was the work. It was not what I had expected. I had high hopes
of working with the scientist who discovered a cure for melanoma.
Although my ideas of scientists and research labs were being disproved,
I held fast to my breakthrough vision of the scientific process.
I would be working in the lab for ten weeks. Surely that was long
enough to see at least five or six major scientific discoveries.
a litter of baby mice
As a science-communications
intern, of course, the research I did was pretty rudimentary. Under
Yu's careful observation, I was given a litter of nine mouse pups
only fourteen days old. My job was to determine their genotypes,
or genetic makeup. Every trait has a genotype and a phenotype .
My assignment was to determine whether my mice had two specific
genes: MIP-2 (the mouse MGSA) and P16 (a tumor-suppressing gene).
In order to
check for each gene, I had to understand simple genetics as well
as a scientific process called transgenics.
each pup's P16 genotype, I checked for the combination of alleles
the pup received from its parents. Each gene in a creature's body
comes in two forms or alleles. We get one allele from each parent.
The two forms are either dominant (+) or recessive (-). So, we can
get a dominant allele from each parent (+/+), a recessive from each
parent (-/-) or one of each (+/-). In the case of fur color of mice,
a relatively straightforward example, the dominant allele might
code for black fur (+/+), the recessive for white fur (-/-), and
a mix of the two yields brown fur (+/-). During mating, each mouse
passes on one copy of its two alleles. The trick with mice is to
breed two mice so you get the right combination of alleles for a
specific gene .
In my case, both parents were (+/-) for P16.
In order to
determine the MIP-2 genotype for the pups, I worked with transgenics.
Transgenic mice are mice that have had foreign genes incorporated
into their DNA. The result of the foreign DNA is an overactive gene.
In this study, the mice were transgenic for MIP-2. My litter had
a mom with no foreign MIP-2 added, and a dad that had foreign MIP-2
In order to
see each gene's effect on skin cancer we needed to know which pups
got which alleles. For example, mice with a regularly active MIP-2
gene may not get skin cancer or mice without P16 may get it twice
To find out
which mice are which, I took a tiny bit of skin and used special
chemicals to digest away everything but the DNA. The DNA was run
though a process called a polymerase chain reaction, or PCR. In
PCR, the double stranded DNA is heated just enough so that it opens
up and can be copied. Researchers can regulate which sections of
the DNA will be copied and therefore they know the size of the section
that is copied. By doing this repeatedly, thousands of copies of
a specific section of DNA can be produced. The multiplied DNA is
then mixed with a loading dye and put onto one end of a gel-a material
with the consistency of Jell-O spread into a sheet about ¼ inch
thick -and electricity is run though it. The electric current pushes
the DNA molecules through the gel. Lighter pieces of DNA molecules
move faster and so travel farther than the heavier ones. Once the
gel has run for several minutes it is viewed under ultraviolet light.
in the gel causes the DNA to fluoresce, revealing its position.
Since an investigator knows exactly how big each portion of DNA
should be and has a positive control that shows the position of
the dominant and recessive alleles, the test identifies what a particular
gene is and whether the mouse is (-/-), (-/+), or (+/+).
the difficulty of the simplest lab procedures
Now all of this
seems pretty easy, right? Wrong. I have never messed up anything
as much as I messed up these procedures. In yet another blow to
my predictions, I realized that scientific procedures are not instantly
learned. Yu very patiently tried to teach me techniques of slowly
and carefully adding chemicals to the nine tiny tubes holding the
skin that was to be digested from each mouse. She brought the different
liquids into her pipette and out again with equal smoothness, exactness,
and precision, whereas I sucked chemicals in too quickly getting
air bubbles that ruined my measurements and then splattered the
liquid as I shot it into tubes leaving unknown amounts of chemicals
in tiny droplets all over the nine tubes, the bench and my lab notebook.
My aching hands
failed to hold the pipette steady…sometimes to the extent of sending
a tiny plastic tube flying and forcing me to start over. Once I
finally succeed in performing an acceptable digestion, I placed
my DNA in the PCR machine and then ran a gel. I didn't discover
until afterward that I had forgotten to actually take the DNA from
the PCR machine and add it to the gel, instead I had only run the
loading dye. When I tried again, I ran the gel without the positive
control so the results were incomprehensible. With each clumsy mistake,
however, I learned a little more about science and much more about
scientists. Richmond and her colleagues reacted to many of my mistakes
with laughing reminiscences of similar mishaps that they had experienced
as young researchers. Each story bolstered my self-esteem and undermined
another stereotype. I realized that scientific research demands
skills that must be learned rather than skills that are innate.
My visions of child prodigies doing experiments on the playground
were replaced with real scientists who made mistakes and learned
from them. No one is born a researcher. True, some people are gifted
in scientific thinking, but even they were not born with a steady
pipette hand…much less a working knowledge of biochemistry.
beauty of DNA
I made many mistakes, I did get some experiments right. The first
time I did a digestion correctly and the silvery threads of DNA
became visible through the plastic walls of the test tube was amazing.
I had no idea that DNA can actually be seen with the naked eye.
But it was there, in my little tube exposed by a concoction of chemicals
that my shaky pipette had miraculously delivered in the appropriate
amount. It was an impossibly thin strand curled and knotted and
suspended in solution for me to see. It was diamond-like and sparkling
and beautiful. Maybe DNA does not always look like that to everyone.
Maybe it is only beautiful to novice researchers and those who truly
love science. But I was amazed. I was so proud that I did not want
to put it in the PCR machine.
When I finally
finished an entire experiment that worked and I had the P16 genotypes
for my mice, I was again amazed. Not only did I know the genes of
these mice, but I knew them because I had figured them out! My breakthrough-a-week
idea of science, however, was faltering. Science is full of wide-eyed
astonishing moments that amaze the new researcher and drive the
more experienced ones. Yet true "breakthroughs" are very rare. Although
my discovery of the P16 genotype of nine mice pups thrilled me,
it was far from a breakthrough. What took me a month to learn would
have taken Yu a few days to complete without incident. A few years
ago the technique I learned was a breakthrough, but now it is a
familiar technique that thousands of scientists around the world
are using every day in their efforts to solve new puzzles related
to the basic machinery of life.
While much of
my time was spent with Yu doing and redoing procedures, I also spent
a lot of time with Richmond and the postdoctoral fellows talking
about science and why they chose to dedicate their lives to research.
With each conversation, the lab coat, glasses and other preconceived
notions were peeled away revealing wonderfully interesting people
with lives and families outside of the lab and years of hard work
to their credit. All of the people are brilliant, but I learned
first hand just how hard they have worked.
As I became
slightly more skilled and began to talk to the scientists around
me, I noticed that, although scientists spend most of their time
doing scientific research, there is also much eating, drinking,
talking and laughing. As a lab we had birthday parties, wedding
showers, baby showers, 'Welcome to the lab' parties and 'Good luck,
we'll miss you' parties. We went jet skiing and white water rafting
together. I met people's husbands, wives, fiancés and children.
is different and every one has a story to tell. I met families struggling
to obtain visas to stay and work in the US. I met couples who shared
their life's ambitions to work in science. I also met men and women
who had made astounding sacrifices of time and family to carry on
the research they considered important. There's the child whose
second word was "oncogene"
(his first was "McDonalds"), and there are also the kids who have
no idea what mommy or daddy does for a living.
In the lab I
saw my very first Chinese newborn. I had the opportunity to attend
my first Hindu wedding. I met a breast cancer survivor who is now
devoted to scientific research and breast cancer awareness. The
men and women in the lab are all so different, but they share one
thing in common. They love their jobs.
By the end
of the summer, my mad scientist idea was a dusty memory. The people
I met were truly regular, every day people. They go to work and
come home just like everyone else. They get sick and their kids
get sick and they have tough problems at work that they need to
figure out. They are also vibrant, dynamic and captivating. One
difference, however, is that they probably can't really discuss
those problems with many outside friends.
"hypothesis" about the nature of science and scientists was far
from correct, but through careful observation I was able to see
where my logic was flawed and make adjustments. I learned so much
about science during my two months in the lab but I also learned
a lot about scientists. When my two months were over I had a whole
new set of prejudices in place; views of researchers as amazingly
brilliant, insightful and dedicated people who love their work and
are committed to a higher calling: the never ending search for knowledge.