What if you were diagnosed with a rare kind of cancer, one that was also lying in wait for other members of your family?
And what if you had the opportunity to advance research in that very same cancer?
Wait, one more thing: You're a high school student.
In the winter of 2006, Alex Royce was a sophomore at Mount Desert Island High School, the closest secondary school to The Jackson Laboratory. When he and his classmates were assigned to find a day's job shadow in a research facility, Alex picked the Laboratory because, he says, "I thought the Lab looked pretty cool and wanted to know what was going on inside it." Alex also had an interest in science, especially engineering.
Alex is a tall, soft-spoken boy with a British accent and a friendly, easygoing demeanor. His family, originally from England, moved to Bar Harbor from Holland in 2005 to explore new opportunities for his stepfather's 12th generation mussel-farming business.
Greg Cox, Ph.D., volunteered to host Alex on his job-share day. Dr. Cox studies neuromuscular disorders such as amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) and muscular dystrophies. He's also well known as a fun dad of three young boys and a caring mentor to the postdocs and technicians in his laboratory.
"That first day in the lab was a blast," Alex recalls."I had imagined the scientists would all be the serious type like in the movies: grumpy, no sense of humor, just concentrating on doing work and getting results. And yes, they were working, but they were also having a lot of fun and joking around."
Dr. Cox, his office shelves decorated with a miniature Oscar Mayer Wienermobile and other goofy toys, says that Alex fit in with his lab group right away. "At the end of the job-shadow day, I invited him to join the lab as an academic-year intern for the next school year, and he agreed."
A turning point
Soon after Alex started his internship in fall 2007, he and Dr. Cox began considering what his research project would be. But if life is what happens when you're making other plans, as John Lennon used to say, life—at its most unpleasant—happened.
An avid runner, Alex noticed he was sweating excessively when out for a run and, more disturbingly, could hear his own heart beating too loudly. A series of medical tests revealed a large tumor around his aorta, the major artery leading from the heart. Surgery to remove the tumor was scheduled right away.
Subsequent genetic testing of Alex, as well as three other family members, revealed that they all have a rare, dominant genetic mutation that causes a cancer called familial paraganglioma (FP). This diagnosis means they are likely to develop tumors around the head, neck, heart and abdomen. FP patients must have frequent scans to detect tumors as early as possible, but even then tumors may develop where they are difficult or impossible to remove, or become malignant.
Through Alex's medical ordeals, Dr. Cox stayed in close contact with him and his family. "Alex was already part of our lab group and we felt connected to him," Dr. Cox says. "Not surprisingly, they had a lot of questions about the cancer: how is it inherited, and what are the ramifications for the other members of the family? And even though FP is outside of my primary area of research, as a genetics investigator I was able to do a lot of background research in the disease much more easily than a non-scientist."
After looking through the literature and reviewing the research that had been done on the cancer, Dr. Cox was struck by an important detail: "There were no mouse models available to study familial paraganglioma."
How to make a new research model
At The Jackson Laboratory, Dr. Cox and many of his colleagues routinely develop new mouse models for a wide variety of genetic diseases. "So I realized that we could certainly make a mouse model for FP, and that this would be a perfect research project for Alex's internship." At this time Alex was still in the hospital, recovering from surgery, so Dr. Cox relayed this idea to him through his mother, and received an excited "yes" in return.
The human and mouse genome projects of the early 2000s confirmed that people and mice share the vast majority of their genes, and that virtually every mouse gene has a human counterpart. So, mice get the same genetic diseases as humans, for the same reasons. It's also possible to introduce a specific genetic alteration into a mouse that mimics a gene mutation responsible for a human disease. In the case of FP, the genetic mutation was known to be located in a gene called SDHB, so the new mouse model would target the analogous mouse gene.
"Mouse models can be used for a number of different purposes," Dr. Cox explains. "They help us understand the basic biology that underlies a particular disease—the inheritance patterns, how they're transmitted from one generation to the next. They also help us understand the basic molecular mechanisms of what actually causes the disease, and where we might be able to intervene pharmaceutically."
A successful milestone
The prospect of working with Dr. Cox on a research project that could potentially help his own family and thousands of people worldwide who carry SDHB mutations accelerated Alex's recovery from surgery. "He's incredibly enthusiastic," Dr. Cox says, chuckling. "Most of the time we have to rein him in a little because his enthusiasm often gets ahead of where his knowledge base is." To bring him up to speed, Alex says, "Greg got me a grant, three Internet windows and a dictionary." He says the entire lab group was "incredibly helpful and supportive."
Alex is now a high school senior and enjoying life symptom-free. "For college I'm definitely going to pursue something in science," he says. "I want to thank everyone at The Jackson Laboratory for giving me this opportunity. I've lived in three countries, but I've never before heard of high school students interning at a world-class facility, and being able to do their own research projects."
The team has had its first successful milestone: the birth of several litters of mice that are confirmed to carry the mutation that matches the one in Alex's family. According to Dr. Cox, the next step is simply to wait and see whether these mice develop the same kinds of tumors that occur in people with FP. Some FP patients develop tumors at a very young age, as Alex did, but others can live 60 or 70 years before tumors appear. That would compare to a typical mouse age of two years.
"Sometimes you get exactly the same disease symptoms in patients and in the relevant mouse model," Dr. Cox says, "and sometimes they can be quite different. So until we "age" these animals and study the disease process in them, we won't know whether we've got a good model for this particular cancer, even if we know it carries the same genetic mutation that patients carry."
If the team does find a good model for FP, they will try to get drug companies interested in testing compounds on it, in order to identify potential therapies for people at risk of developing the cancer.
Not quite your average high school science project.