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Muriel Davisson examines a Ts65Dn mouse brought out for her to inspect by Louise Dionne. Davisson developed this mouse model to study Down syndrome.

Full circle

by Tom Walsh / Photography by Fran├žoise Gervais

Muriel Davisson faced three career choices in 1959 after graduating at the top of her class at Pemetic High School in Southwest Harbor, Maine.

"There weren't many choices for careers beyond the traditional ones: lobster fishing, school teaching or homemaker," recalls Professor Davisson, now a Ph.D. who, at age 68, is winding down her busy, 38-year career in human genetics research. "Fifty years ago, if you wanted to do something professional, you really needed to go somewhere other than Downeast Maine."

That she did, charting a course that took her full circle. Within three years of being offered a full-tuition scholarship to Mount Holyoke College, a women's liberal arts college in South Hadley, Mass., Davisson was back home on Mount Desert Island, pursuing her fascination with genetics at The Jackson Laboratory.

"I kind of fell into genetics," she says. "I actually majored in the German language and literature my first year in college, and I thought I wanted to go off to the U.N. and be a translator or something. I took genetics as part of a basic biology course that was required at Mount Holyoke. The minute I took the first few lectures in genetics, I knew that's what I wanted to do. I probably wouldn't have come back to the Island until I reached retirement age, but genetics was something that I could do here."

While earning her bachelor's degree, she spent the summer after her junior year at The Jackson Laboratory's Hamilton Station research center under the guidance of Paul Sawin and Richard Fox. That experience as a summer student in 1962 changed her life. "Had they not had grants that gave scholarships to kids, I wouldn't have been able to do that either," she says. "I was able to live at home. At the end of the summer I was asked if I would come back after college to work as a research assistant."

She did, at a salary of $4,300 a year, or about $2 an hour. After working for one year while living at home in Tremont, Davisson decided to enroll in graduate school and to pursue a doctorate. "I realized that I could either be my own boss or I could work for somebody else," she says. "And, in working for somebody else, you may or may not be able to do what you really want to do."

After earning her doctorate at Penn State University in 1969, Davisson returned to Tremont with her husband, Farrell Davisson, a journalist. "When I came back here, I didn't actually have a job at the Laboratory," she says. "I was a geneticist with a specialty in chromosome work. In those days, it was such a small place that, to get a job, you sort of knew somebody who knew somebody. I got a call that there was an opening for a cytogeneticist, and they hired me half time. One thing led to another."

Most of Davisson's long career in genetics research at The Jackson Laboratory has involved finding spontaneous mutations and genetically mapping and characterizing them. Two years ago, she cut back to three days a week after serving for the last 15 years as the Laboratory's director of Genetic Resource Science, which involved management of mutant mouse strains. While she may be part-time on paper, she's as busy as ever. So is her son, Sven, who is now the Laboratory's senior manager of Sponsored Programs.

"More than once, the Laboratory has sent out official letters to the National Institutes of Health that I've signed as the principal investigator and Sven has signed as the institutional official," she says.

Soon after joining the Laboratory in 1971, Davisson began exploring how abnormalities in chromosomes affect development. While geneticists can now manipulate virtually any gene, Davisson says spontaneous mutations are better models of the comparable human diseases they mimic.

"These genetic accidents are still rare, but, in a breeding population of a million mice a year, there are a lot more of them, even though they are rare," she says. "They are like raw material. It's discovery. Every time you discover a new mutation, you don't know where it will take you. You're always learning. That's the excitement of it. And then, if you develop a new model for other scientists to use, you expand the benefit of what your research does for human health. For me, that's a major reason for doing it."

Davisson is best known within her field for developing a mouse model for Down syndrome, a condition related to a chromosomal anomaly linked to mental retardation in more than 350,000 Americans. Over nearly 20 years, her mouse model has proven so essential to research that the National Down Syndrome Society named Davisson the group's 2002 "Researcher of the Year."

"It is the model being used by most scientists who are doing research on Down syndrome and studying behavior, memory and how kids learn if they have Down syndrome," she says. "They can now study this mouse."

As her career winds down, Davisson is looking forward to devoting more time and attention to local history and to seeing the Laboratory from the sea. "I'm learning to sail," she says, "and I'm in my second year as president of the Tremont Historical Society. I like outdoors stuff. I love getting out in the woods with a chainsaw and cutting up fallen trees. With the right saw, one that's not too heavy, I can go all day."

Muriel Davisson loves getting out in the woods with a chainsaw and cutting up fallen trees.

Because the biomolecular complexities of human genetics continue to pose many more questions than answers, researchers at The Jackson Laboratory find it difficult to overstate the scientific value of the Laboratory's Mouse Mutant Resource (MMR) program.

For 50 years, the Laboratory has maintained the world's largest collection of laboratory mice with naturally occurring, spontaneous mutations. This unique repository has a long history of helping researchers around the world better understand the genetic basis of diabetes, obesity, heart disease, neurological disorders and an array of other human diseases.

As mice and humans share the majority of their genes and have physiological similarities, mice are susceptible to many of the same diseases as humans, for the same genetic reasons. Scientists at the Laboratory believe those diseases are best modeled when they occur naturally, as they do in humans.

One spontaneous mutation that occurred 50 years ago remains an important portal on the genetic basis of obesity. The result, a very obese mouse detected at the Laboratory in the 1950s, developed into an excellent model for type 2 diabetes. This mouse model remains in great demand by pharmaceutical and biotech companies now working to perfect new approaches to diagnosing, treating and curing the epidemic of diabetes in America.

Leah Rae Donahue, Ph.D., the Laboratory's director of Genetic Resource Science and current MMR supervisor, asserts that current efforts to create "engineered" knockout mice can't replace mice with naturally occurring mutations.

"In mice with spontaneous mutations, you notice the clinical symptoms of a disease first," she says. "And, when you investigate the genetics behind those symptoms, you may discover a gene that no one suspected was involved with that disease. Spontaneous mutations in the mouse offer the opportunity for true causative gene discovery."

Outside researchers benefit from the mice that have been discovered, characterized and distributed by the MMR. Kathleen Millen, Ph.D., an associate professor in the Department of Human Genetics at the University of Chicago, relies on spontaneous mutants for her research into cerebellar development.

"I have studied several cerebellar classic mutants, including weaver, staggerer, lurcher and others," Millen says. "These spontaneous neurological mutants are an invaluable resource and have been the basis of many of the major insights into cerebellar development by the research community over the last few decades."