Footnote #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.
Footnote #2
Students who have completed their Ph.D.’s.
Footnote #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.
Footnote #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.
Footnote #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.
Footnote #6
"Oncogene" is a generic term for a gene that causes cancer.

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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 Click to open footnote, then click again to close 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.

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 fellows Click to open footnote, then click again to close, 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 phenotype Click to open footnote, then click again to close. 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 two mice so you get the right combination of alleles for a specific gene Click to open footnote, then click again to close. 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 ingredient Click to open footnote, then click again to close 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 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" Click to open footnote, then click again to close (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.

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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Interview with Allison Byrum

Ann Richmond's laboratory gains new insights into tumor growth and wound healing through studies of the "SOS gene"