C. Richard Boland, MD ’73, made it his mission to identify the cause of the hereditary colon cancers that plagued his family. He succeeded, uncovering the genetic basis of the disease, now known as Lynch syndrome. During his decades of research, Boland was buoyed by a strong desire to help his family and others impacted by the disease. Today, thanks to his scientific contributions, there are diagnostics and treatment guidelines to save the lives of those with or at risk for the disease.
Appeal of YSM
When considering where to apply to medical school, Boland included his father’s alma mater, Georgetown Medical School, on his list. A strong candidate, Boland was accepted. But before responding to Georgetown, Boland wanted to learn more about Yale School of Medicine (YSM), where he had also applied, at the suggestion of an advisor. He was invited to interview with a YSM alum who lived near the University of Notre Dame, where Boland was studying, and jumped at the opportunity. After the interview, Boland decided he wanted to go to YSM.
“I liked the thesis idea, and I liked the idea that YSM didn’t have tests,” he says. “The real attraction was that I was going to get a chance to do research. I recognized that in the world of science, research is critical. I wanted to get a sense of how you look at, interpret, and incorporate data.”
An acceptance letter from YSM soon followed, and, with his parents’ blessing, Boland enrolled.
Family Medical History
A pivotal event occurred the summer after Boland’s first year at YSM. Boland’s father died of colon cancer. It was his second bout with the disease.
This motivated Boland to begin looking into his family’s medical history. He found multiple cases of colon and other cancers. He says, “I realized that something was really wrong. Something was going on that wasn’t in any of the textbooks. The family did not have the one form of familial gastrointestinal cancer that was known then.”
Boland discussed this with his professors, who said, “If you think there’s something else here, go out and prove it.” That was all Boland needed to hear. He elected to focus his thesis on studying his family’s medical history and trying to find the cause of the colon cancers.
Impactful Thesis
Boland’s thesis research involved doing blood and other work on himself and relatives and mapping the family’s medical pedigree. However, because technologies capable of linking a disease to a specific gene were not available then, Boland’s research, which described a disease, did not reveal the precise cause of his family’s colon cancers.
Boland admits, “My thesis research was a failure, in a way, but it got me thinking about what was going on. It also allowed me to get into communication with epidemiologist Henry Lynch, MD, who had earlier documented families similarly affected by colon cancer.” Lynch had called the disease he observed cancer family syndrome and then hereditary nonpolyposis colorectal cancer (HNPCC). In 1997, after the genetic cause of the disease was discovered, Boland chaired the international conference that renamed the disease after Lynch: Lynch syndrome. It is the most common form of hereditary cancer.
Following Boland’s graduation from YSM in 1973, he continued his research in earnest on his and other families. That work took off in the late 1980s, when techniques for genetic cloning and sequencing blossomed. Boland took a sabbatical to learn how to do genetics research and subsequently shifted his focus from glycoproteins (his initial work) to genetics work. In the early 1990s, Boland was working on discovering the genetic alterations involved in stepwise cancer formation, and the order in which they occurred. As he worked on this, he started using microsatellite analysis to solve this problem. Serendipitously, in 1993, three other labs discovered that alterations in these sequences occurred in a subset of colorectal cancers, which led to the recognition of the genetic basis of a subset of colorectal (and other) cancers, including all of the Lynch syndrome families. This discovery led Boland’s lab to develop the first laboratory model of Lynch syndrome, and by 2001, Boland’s lab made the first diagnostic test for the syndrome in his family. These advancements had life-saving implications.
Boland offered the test to all his family members. Twenty-two of those tested had the Lynch syndrome mutation, and of those individuals, 21 are alive and cancer-free today. Previously, nearly all mutation carriers had died of cancer because no one knew if they carried this risk, and there weren’t effective ways to prevent the Lynch syndrome cancers. All that has changed since.
Thanks in part to Boland’s groundbreaking work, today there are advanced, new tests that can easily determine if someone has Lynch syndrome or something like it. Boland says, “There are simple tests on the tumor tissue that will tell you exactly what gene is affected, which leads to finding what the mutation is. Related family members can then get tested. And there are guidelines for how to monitor or treat Lynch syndrome.”
Gratitude
Boland, now retired and enjoying serving as an officer in the UCSD Emeritus Association, giving lectures occasionally, and spending time with family, is grateful for many things.
He is grateful that YSM provided him with a scholarship and a loan after his father’s death, when his mother told him she could not afford to pay his tuition.
Regarding his career, Boland is most grateful for solving the Lynch syndrome problem—for his family members who have passed, those alive today, and future generations. He notes, “I speak with my siblings often and it’s not unusual for them to say, ‘Thanks for all that you did, because we’re still alive and we’re doing well.’ That’s been the best part.”