Angela Belcher Commands a Virus to Hunt a Deadly Cancer

Illustration by Agata Nowicka

An engineer lights up tiny tumors that doctors can’t see.

MIT professor Angela Belcher earned a MacArthur genius grant by engineering a harmless virus to form tiny wires — an insight that could lead to cheap and biodegradable batteries and solar cells. Now she’s using the same virus to perform a different trick and solve a very different problem: the grim prognosis for women with ovarian cancer.

Today when surgeons remove ovarian tumors, they do it by eye. It is an inexact procedure called “debulking,” which can be as devastating as it sounds: the doctors sometimes need to remove parts of a woman’s colon, bladder, and other organs. Even so, they often miss small tumors that seed the cancer’s recurrence. That’s a large reason why ovarian cancer has one of the lowest survival rates. Fewer than half of the women who develop it survive more than five years.

That’s where Belcher’s system comes in. She’s come up with a way for doctors to see even the tiniest cancer cells on a screen, in real time, during the procedure. She’s done this by tuning that virus so that it binds to and lights up tumor cells that have spread beyond the ovaries.

Mice that underwent surgery with Belcher’s approach lived 40 percent longer. That’s a big deal. Michael Birrer, who is head of the UAB Comprehensive Cancer Center in Alabama and worked with Belcher when he was at Massachusetts General Hospital, thinks the success in mice will translate well into people. While no formal application has been filed with the Food and Drug Administration, Birrer says he has been talking to agency staff about gaining approval to try the approach in women. “I think for ovarian cancer, it’s close to prime time,” Birrer says.

Unfortunately, Belcher’s technique can address only one of the reasons ovarian cancer is so deadly, which is that often it’s detected too late, after it’s already spread too far. At least for now, her technology is not able to detect cancer in the first place. Instead it’s about improving the prognosis for women who have surgery.

For the original application of this technology—making a virus churn out wires for batteries and solar cells—Belcher tweaked its DNA so it would bind to semiconductor particles. For the cancer probe, she engineered the viral DNA so it does something different: it expresses proteins that bind both to carbon nanotubes and to proteins produced by cancerous cells.

First the virus is put into a solution containing nanotubes so they attach to each other. Then this combined virus-nanotube payload is injected into the body. There it will attach to cancerous cells and avoid healthy ones because they don’t produce the target proteins. As for the nanotubes, they will fluoresce when hit by infrared light, so when an infrared camera takes a picture of the tissue, the glow of the nanotubes marks the locations of the tumors.

In a recent talk at the Dana-Farber Cancer Institute in Boston, Belcher showed a slide with scans of two lab mice. One scan, on a cancer-free mouse, was black; the other was studded with spots of light — tumor cells that a surgeon working without Belcher’s virus-nanotube probes had missed. Belcher says that after getting mice to live 40 percent longer after the ovarian cancer surgery, “I was excited and said ‘good job’ to my students. But I want it to be 80 percent.”

The findings have not yet been published, but they’ve been submitted to a journal and are under review.

The outsider

Belcher’s work in biomedical engineering is part of a promising trend. As she points out, “I’m not a real biologist.” Typically, engineering and medicine “have been kind of separate cultures,” says Stephen Boppart, who directs the Center for Optical Molecular Imaging at the University of Illinois. “We are seeing more and more engineers and data scientists starting to apply their skills and talents and problem-solving abilities to problems in medicine and to health care,” Boppart says.

Prior to joining MIT’s Marble Center for Cancer Nanoscience, Belcher, 50, worked in energy and nanomaterials. A shelf behind her office desk contains a collection of seashells and chunky calcium carbonite crystals. Those natural materials offered clues that led to her success in building new materials from scratch. She did her Ph.D. research on how abalones grow complex and strong shells by producing proteins that meld with ingredients found in seawater.

“The surgeons were skeptical of the molecular stuff.”

When she first considered applying her ideas in biomedicine, “I wasn’t sure I could contribute, and I didn’t want to take up the space,” she says. “But my collaborators convinced me that this is a good disease to work on.”

Birrer, the oncologist in Alabama, says Belcher’s outsider perspective was crucial. “When we first proposed this, everyone said surgery and ovarian cancer had been talked about for a long time and there’s not a lot we can do to change it,” he says. “The surgeons were skeptical of the molecular stuff.”

Belcher also still does energy research, engineering viruses to generate materials that could be used as part of low-carbon energy systems. She teaches, promotes science in grade schools, and tends to two boys whom she describes as her “favorite biomaterials.” But the ovarian cancer research is not just a one-off. She’s working on improving the efficiency of the technology, extending it to other kinds of cancer, and possibly developing a diagnostic tool or screening tool for high-risk women in the future.

“I don’t have the answer,” she says. “But I have the commitment.”

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