Michael R. Tranfaglia ’82 was never just an average Harvard pre-med.

“He was kind of unusual,” says his wife Katherine N. Clapp ’82. Her first memories of Tranfaglia include a characteristic Marine Corps haircut acquired during a summer spent in boot camp “just for an experience,” and another summer souvenir—a single sunburned side picked up during a cross-country bike trip and debuted the following fall.

While at Harvard, Tranfaglia kept himself busy with a concentration in biology, an unofficial minor in psychology, and a host of extracurricular sporting activities.

Michael R. Tranfaglia '82

He says he was a young man with no “great aspirations” as a collegiate, simply wishing to become a small town psychiatrist with a comfortable middle class life. However, he says, those modest plans “jumped the tracks big time” about 10 years after commencement, when Tranfaglia and Clapp learned in 1992 that their first child, Andrew, had Fragile X syndrome.

Fragile X is a genetic disorder resulting from a mutation on the X chromosome, and according to the Centers for Disease Control, the disorder is “the most common known cause of mental retardation and developmental disability that can be inherited.”

A FRAGILE X FOUNDATION

Tranfaglia and Clapp were left frustrated as they brought a then three-year-old Andrew from pediatrician to pediatrician—repeatedly failing to find someone who could successfully diagnose their son’s developmental problems. Though the doctors tested Andrew for a number of conditions, none of these preliminary screenings could provide the answers the family was looking for.

“Fragile X is probably the first thing they should have tested for, but it really was missed in the first couple of passes,” Tranfaglia says.

For a genetic disorder, Fragile X is quite common—affecting one in 4,000 males and one in 6,000 females—says Tranfaglia. However, he says, at the time, familiarity with it was limited even in medical circles.

Upon receiving the Fragile X diagnosis, Clapp and Tranfaglia set out to educate themselves about the disorder.

“I’m a psychiatrist, so I had heard of [Fragile X], but I had never actually seen a patient with it,” Tranfaglia says. “In textbooks, mentions were so brief that they were almost meaningless...I had heard the term bandied about, but not discussed in any meaningful way.”

Yet the more Tranfaglia and his wife learned about the disorder, the more compelled they felt to help address this gap in knowledge.

The couple, with the help of Kathy May (another Fragile X parent), founded FRAXA in 1994, a nonprofit foundation that aims to broaden biomedical research efforts dedicated to finding better treatments and possibly a cure for Fragile X, says Tranfaglia.

Since its founding, FRAXA has capitalized upon technological advances ranging from the booming biotech industry to the advent of the internet, allowing it to develop a large but diffuse community of Fragile X parents and researchers dedicated to the study of the disorder.

According to Tranfaglia, in the early 1990s the idea that the disorder could be treated at all was controversial, as its main symptom is mental retardation. With mental retardation commonly perceived as irreversible and largely untreatable, many are reluctant to seek medical treatment for it, Trafaglia explains. Many are inclined to view Fragile X as “just the way these kids are,” he says—an inclination FRAXA looks to combat.

SEARCHING FOR A CURE

FRAXA gathers donations primarily from personal contacts of Fragile X relatives, and—in turn—considers research proposals submitted by scientists looking to receive these funds from the organization.

Proposals are reviewed by the foundation’s volunteer Scientific Advisory Board—a body made up of 20 prominent scientists, including Harvard Provost Steven E. Hyman. The board claims three Nobel Laureates—James Watson, Eric Kandel, and Susumu Tonegawa—among its members, as well as “several future winners,” says Tranfaglia.

“We’ve been so successful on the science that we’re in a phase now where we’re transitioning; raising the bar on what we’ll fund,” Tranfaglia says. “We’re only funding translation research...designed to translate basic science findings into clinical applications.”

He adds that a goal for the near future is to work closely with pharmaceutical groups to develop actual treatments for the disorder and bring them to clinical trial.

Fragile X is caused by a mutation of the FMR1 gene on the X chromosome. The gene regulates synaptic plasticity in the brain—the ability for neural connections in the brain to adapt over time as a result of experience. Plasticity is thought to be especially important in the areas of learning and memory.

A possible solution to the disorder—the replacement of the defective gene with a normal copy—has proven difficult to make a reality, as scientists have yet to find a way to physically place a new copy of the gene into brain cells.

At present, FRAXA-funded researchers have made progress in identifying the signaling pathways in the brain that are disrupted because of Fragile X-caused genetic mutations. If these disrupted pathways can be brought back to normal with drug treatment, a wide array of autism spectrum disorders that share in their pathology this interrupted signaling pathway may be treatable.

“Autism folks are skeptical that [Fragile X and autism] are related, but as a psychiatrist, the first thing you realize is that there are a lot of people who look and act like they have Fragile X, but don’t have it,” Tranfaglia says. “By identifying this pathway, we can also identify ways of testing those other folks to see who might respond to those same treatments.”

A GLASS HALF FULL

Since FRAXA’s founding, Fragile X “certainly has become better known and better understood in some circles,” Tranfaglia says. Pediatricians are diagnosing the condition earlier and special education specialists are better understanding how to address it, he says.

Nevertheless, Fragile X still has yet to receive the public address it may warrant, in large part because of the overarching stigma associated with mental retardation, Tranfaglia says.

“There really is a bias against mental retardation, and that bias is actually more common in the higher strata of society than in the general population,” he says. “I know of other physicians and psychiatrists who have kids with Fragile X, and they don’t want to step forward and be counted because they’re afraid of the stigma, that it somehow reflects badly on them.”

As a result of his experiences, Tranfaglia advises current undergraduates to “push themselves in ways they might not expect.”

“Don’t be afraid to try, even if you’re not great at it,” he says. “You have to be flexible, adaptable, able to take on new challenges.”

Clapp recalls how her husband always pushed the boundaries. Their first real date, she says, was an 85-mile biking trip to a cabin in New Hampshire.

“He liked adventures like that,” she says.

Former roommate Jeffrey T. Wu ’82 recalls a young man that always seemed to take things in stride, citing Tranfaglia’s appreciation of dining hall food amidst a sea of complaint from peers. Classmates always “got a kick out of Mike because he was so unfussy,” Wu says. “He would always say ‘Mmm...not bad.’”

“I think he has approached a lot of his life that way—he was a glass-half-full sort of person, and that has carried over to what he has done,” Wu says. “When Mike and Katie learned what Andy was up against, a lot of people would have felt bad for themselves, and seen obstacles—and I’m sure he did see those at first—but what he also saw was opportunity to do something significant.”

A FAMILY MAN

Tranfaglia, Clapp, and their two children—Andrew, 17, and Laura, 15—live about 40 miles outside of Boston in West Newbury.

According to Laura Tranfaglia, her father is “smart,” “helpful,” and “always seems to be right.” She says her father is also quite the multitalented individual—with interests ranging from carpentry to cooking to playing with remote controlled cars with his son.

Laura Tranfaglia says that in his downtime, her father can often be found watching “Mythbusters” or playing fighter-jet computer games.

“He wanted to be a pilot, but decided to be a doctor instead,” she says. “It’s ironic because he would be killing people as a fighter pilot, but instead he’s saving people.”

Though living with a brother with Fragile X has been tough at times, Laura Tranfaglia says, medical advancements and the simple passage of time have made her brother’s condition more manageable.

“I guess I really wouldn’t understand people like him as much—I wouldn’t see them as as normal as I do now,” she says.

Also, she jokes, “It’s the reason why I have an ‘A’ in biology.”

—Staff writer Aditi Balakrishna can be reached at balakris@fas.harvard.edu.