About five years ago, Steve Murray arrived with his family in Bar Harbor, Maine, to start a new chapter in their lives.
For Dr. Murray, a newly minted Ph.D. biochemist, The Jackson Laboratory offered a challenging research position using mouse genetics. And he and his wife Rebecca, emerging from urban Boston, thought Bar Harbor looked like a good place to raise their 4-year-old son and yet-to-arrive daughter.
Dr. Murray began work as a postdoctoral fellow with Professor Tom Gridley, whose lab investigates the intricate mechanisms that direct early development and growth. But soon life for the Murrays was forever changed by a different kind of developmental anomaly. Rebecca's routine ultrasound turned up a disquieting image. Genetic tests revealed that both parents were carriers for cystic fibrosis, and tests confirmed that their unborn daughter had the disease.
Five years later, Dr. Murray is excited about a new development that promises to improve CF research, a mouse that models the disease's impact on the lungs. As a scientist, he explains the research involved, but as a father his goals extend far beyond his lab.
"I'm in a position to help the human condition," Dr. Murray reflects. "I can improve mouse models and help bring them to other researchers, which will make pre-clinical testing more effective. I'm also looking to build relationships with other CF research groups and help create synergy in the effort. But in the end, it's about translating the research to human medicine."
A different kind of development
Dr. Murray is affable and soft-spoken, but his piercing intelligence is quickly apparent. The terms and concepts of his work come thick and fast, easy and familiar in his world, but leaving the non-scientist sprinting to catch up.
After receiving his bachelor's degree in biology at highly regarded Carleton College in Minnesota, Dr. Murray headed east to work as a research assistant, then entered a Ph.D. program in biochemistry at the Boston University School of Medicine. His work there consisted mostly of studying "cells in a dish."
His move to postdoctoral work with Dr. Gridley was a logical next step in what was, to that point, a fairly typical progression for a promising young scientist. He settled into the grueling postdoc routine of intensive bench work while supporting his young family.
Then came the news that was to shape Dr. Murray's outlook and future path. Learning about their daughter's condition before she was born, while traumatic, eased some of the transitions that awaited the family.
"Most children aren't diagnosed until they're two or three years old," says Dr. Murray. "There's no way I can know for sure, but I think it was very helpful for us to know before Maggie was born. We were able to work with a genetic counselor and raise issues beforehand so we could have everything properly arranged for her."
Maggie stayed in the hospital for 13 days and had surgery soon after birth. But she thrived after that and had few complications as she progressed through toddlerhood. The Murrays felt some pressure to relocate somewhere near a major medical center for Maggie's care, but Dr. Murray stayed with his postdoctoral work.
After his final paper as co-author with Dr. Gridley appeared in the prestigious Proceedings of the National Academy of Sciences (PNAS) in 2006, Dr. Murray faced some important decisions. As he pondered how he wanted to proceed, he reached some not-so-typical conclusions.
"I tested the waters a bit in the faculty job search market, but I'm not a lung biologist. It would take quite a long time to learn the nuts and bolts of the field and get my own program. Also, we didn't want to move—we had become attached to Downeast Maine. Maggie was receiving topnotch care. We are fortunate that there are great doctors in this area. So I was unsure of exactly what I wanted to do."
Finding his way
The opportunity to make a difference and stay in Bar Harbor came at a perfect time. A position opened in Genetic Resource Science (GRS) at the Laboratory about a year ago, just as Dr. Murray was finishing his postdoc and considering his next career move. While it didn't provide him with his own laboratory, it did significantly speed his ability to contribute to CF research.
Among his other tasks, Dr. Murray is working to develop a cystic fibrosis repository. The repository would gather mouse models for CF in one place, fully characterize their genetic backgrounds and mutated gene(s), and make them available to biomedical researchers. Dr. Murray is aware of 15 or so different mouse models for CF that have been used in published work, but they are scattered in different laboratories and are not easy for other researchers to use. The repository would be a boon to the CF research field, providing a resource for research and a hub through which scientists can interact.
The CF mouse that excites Dr. Murray is from a group at the University of North Carolina. Helping to build relationships with other institutions and create a collaborative effort is a big part of his goals for the repository.
With his own research, Dr. Murray hopes to address three crucial needs. The first is to improve the new mouse model by altering its genetic background, mitigating both the age of onset and severity of the disease. Second, because different patients with the same mutation in the CF gene (CFTR) can have very different disease progressions, he is looking to define the genes that affect disease progression. It is these genes that could be ideal targets for future drug development. Finally, he wants to provide pharmaceutical companies with the ability to test new drugs in a variety of genetic backgrounds.
"Testing drugs in different genetic backgrounds would improve drug development," Dr. Murray says. "It would also prevent a lot of wasted time and resources spent on developing drugs that might work well in a particular strain but are ineffective or dangerous with other genetic backgrounds."
A balancing act
Today, Maggie is a bright 5-year-old who plays, swims and dances with her peers. Common colds and other illnesses are significant challenges to CF patients, so coordinating her activities is a fine balance that her parents have mastered well.
"On the one hand you want to protect and shield her," Dr. Murray says, "but you also want her to have fun and be a kid. Maggie is doing well, active and happy, and that's what counts."
Her father is coming to terms with balance in his life, too. Outside the Laboratory, Dr. Murray is active in the Cystic Fibrosis Foundation, working with fellow employee Woody Leighton, who founded the local chapter years ago after his daughter Katie was born with the disease. Katie is now in college, and the Leighton and Murray families collaborate on the annual Great Strides Walk fundraiser. At the Laboratory, Dr. Murray toils to push CF research progress forward. But at the end of the day, he stops his work, sets other things aside—and plays with his children.
"Ever since Maggie was born I've wanted to go into CF research, and a lot of PIs [principal investigators] in the field have a personal connection to the disease. My wife and I have thought about and discussed the wisdom of me going into work that can become so all consuming. The CF repository is a part of my job now, not all of it, and that's probably a good thing."
Understanding cystic fibrosis
Cystic fibrosis, or CF, is a fatal disease, but the prognosis is far better than it was 50 years ago. At that time few children lived into their teens, but advances in clinical research and treatments now make it common for people with CF to live into their 30s and beyond. Of course, the ultimate goal of research is to find an outright cure, but continued progress in managing the disease already holds the promise of a much brighter future.
CF is caused by mutations in a gene called CFTR. The CFTR gene is important for establishing the proper flow of water and chemicals in and out of cells. Mutations in CFTR can disrupt this flow, leading to widespread consequences. The immediate effect is on the body's production of mucus, the viscous, slippery substance that lines and protects our airways, digestive system and other tissues.
People with CF produce mucus that is abnormally thick, leading to problems in the organ systems in which mucus plays crucial roles. The most prominent symptoms involve the lungs, where mucus accumulates and sometimes obstructs the airways. This causes breathing difficulties and encourages bacterial infections. The abnormal mucus can also interfere with pancreatic duct function, leading to digestive problems.
While it has been well established that CFTR causes the disease, other genetic factors are thought to strongly influence its severity and course. The CFTR mutation affects different people in different ways, indicating that a person's genetic background, including mutations in genes other than CFTR, probably contributes to moderating or exacerbating effects. Environmental factors are also likely to play a role, although the exact causes and effects are still not entirely clear.