By figuring out how our DNA fixes itself up after it’s injured, Leona Samson hopes to bring us closer to the time when treatments for cancer and other ailments can be custom-tailored to individual patients.
Samson, a professor of both biology and biological engineering, and head of MIT’s Center for Environmental Health Sciences, is a toxicologist. This means her interests include the factors — ultraviolet radiation, selected chemicals, components of cigarette smoke — that can trigger cancer.
Samson’s specific focus is DNA repair. The process begins when the DNA in a cell sustains damage. (This happens spontaneously, but it’s also caused by those “environmental insults” toxicologists specialize in.) The DNA repair machinery quickly goes to work and, most of the time, fixes the damage.
We can be grateful this capability exists. “The connection between deficiencies in DNA repair and cancer,” notes Samson, “is absolutely clear.”
The faculty member has extensively explored DNA repair, along the way making key discoveries. It used to be thought that when your body is exposed to a cancer-causing substance, 20 or so genes in the cells affected are turned on. But her group showed that environmental insults can affect several hundred or more genes at a time.
The finding complicates life for people trying to combat malignancies. But Samson argues that “we’ve got to embrace this complexity if we hope to put the pieces together in a way that lets us be predictive about problems like cancer.
“The work may also yield medical advances long before the hugely complex picture of how genes react to different insults is complete. Samson, in fact, is working on a technique that could help cancer patients by letting doctors predict whether a particular type of chemotherapy will work in a specific case.
INDIRECT ROUTE
That Samson’s an expert on such topics is a happy accident. Born into an English family with no tradition of attending college, she left school at 15 to go to work. One job was as a lab assistant at a pharmaceutical firm near Glasgow, Scotland. “I washed glassware and fed the animals,” she says. She also studied biology at night, and in time entered Scotland’s Aberdeen University to study biochemistry. From there she went on to doctoral work in London under renowned cancer biologist John Cairns.
With Cairns, Samson made vital discoveries about how cells respond to chemicals that cause cancer, which is by expressing genes responsible for DNA repair pathways.
A recent discovery that has caused a stir in cancer circles, meanwhile, grew out of her studies of yeast — a good research model because of its relatively complicated genetics. When her group exposed the one-celled organisms to a cancer-causing substance, about a third of the 6,000 genes a yeast cell is known to harbor were affected, roughly half being activated and the rest being shut down.
The discovery, made possible by a sophisticated genetic testing device called a microarray, amazed the group. “We had so many genes being turned on or off we didn’t really know what to do,” recalls Samson. As she explores the causes of such phenomena, she also says the sheer numbers of genes involved may aid in the cancer battle.
Why? An analogy is boosting the numbers in a public opinion survey pool from, say, 100 to 10,000. A survey with 100 respondents may offer a rough idea of public sentiment on an issue. Having 10,000 lets you probe the nuances of those feelings.
Samson is exploring what can be learned about cells by observing whether identifiable groups of genes turn on when you subject the cells to various insults. This type of testing, dubbed transcriptional profiling, could someday aid patients.
“You can imagine a situation where you’d sample tumor cells, and through transcriptional profiling be able to say, ‘Okay, this person’s tumor won’t respond to this chemotherapeutic agent but it will respond to that one,’” she notes.
As she proceeds with her profiling studies, Samson’s waiting to see if earlier experiments related to DNA repair will prove medically valuable. A colleague of hers, pediatrician David Williams of Cincinnati Children’s Hospital Medical Center, heads a trial aimed at determining whether doses of an anti-cancer medicine can be increased in kids with inoperable brain tumors.
“The body’s most sensitive tissue is the bone marrow,” says Samson, “and as a result, doctors keep tight limits on dosages of many chemotherapy medications.” There’s an alternative — take the marrow out of the body for the duration of a treatment — but it’s not suited to all patients.
Based on lab results, the researchers believe that boosting quantities of specific DNA repair genes in the marrow may do just as well. No one yet knows if the strategy will pay off. Even so, Samson’s happy to be part of the effort: “It’s been quite thrilling,” she says.