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Ten weeks in cancer lab dissolve personal stereotypes
By Allison Byrum / Intern
Dec. 1, 2000
Scientists 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 of 14.
Everyone knows 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 done.
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 act.
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.
Richmond succeeded 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 1 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.
Problems arise 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.
1
A chemokine is a small protein that causes cells to move. Since the characterization of MGSA, a huge
family of chemokines has been discovered and MGSA is a part of that family. Now that so many have been
found, chemokines have “family names” by which they are also referred. MGSA’s “family name” is CXC. So
the gene that codes for MGSA is the CXCL1 gene and the chemokine is simply called CXCL1.
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Ten weeks in cancer lab dissolve personal stereotypes
Richmond and 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 work.
My misconceptions begin dissolving
My stereotypical 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 fellows2, 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.
Yingchun Yu 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 envisioned.
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.
Genotyping 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
phenotype3. 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.
To determine 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
2
Students who have completed their Ph.D.’s.
3 The
phenotype describes outward appearances. For example, your phenotype would include your traits
such as eye color and hair color. A genotype, on the other hand, describes your genes. It would include the
fact that you got a gene for blue eyes from your mom and a gene for brown hair from your dad.
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Ten weeks in cancer lab dissolve personal stereotypes
two mice so you get the right combination of alleles for a specific gene 4. 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 genes added.
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 as fast.
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. An
ingredient5 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 (+/+).
Learning 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
4
If a (+/+) mouse is bred with a (-/-) mouse, all of the pups will be (+/-) since they will get one allele from
each parent. If two (+/-) mice are bred, half of the pups will be (+/-), one-fourth of the pups will be (-/-), and
one-fourth of the pups will be (+/+). In order to check the roles of dominant and recessive alleles researchers
must have (+/-), (+/+), and (-/-) mice available.
5 EtBr, Ethidium Bromide, is a chemical added to the gel that mixes with the DNA so that it will glow under
ultraviolet light. Since EtBr mutates any DNA, it is important for scientists to wear gloves when handling gels.
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Ten weeks in cancer lab dissolve personal stereotypes
thinking, but even they were not born with a steady pipette hand…much less a working
knowledge of biochemistry.
The beauty of DNA
Even though 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.
Every family 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” 6 (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.
6
“Oncogene” is a generic term for a gene that causes cancer.
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Ten weeks in cancer lab dissolve personal stereotypes
My original “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.
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