March/April 2008

Engineering Cures

MIT researchers meld biology and engineering in the fight against cancer.

By Katherine Bourzac, SM '04

Credit: Mutt Ink

Don't ask Sangeeta Bhatia, SM '93, PhD '97, whether she's a biologist or an engineer. For her, the question is beside the point, as it is for all the other MIT professors who use the tools of both engineering and biology to study cancer. "When one focuses on human disease, there isn't a real boundary between science and engineering and medicine," says Bhatia, an associate professor who is developing nanoparticles for monitoring and treating cancer.

Bhatia is one of many MIT researchers who will benefit from the establishment of the new David H. Koch Institute for Integrative Cancer Research. This fall, David H. Koch '62, SM '63, gave MIT $100 million to fund research that brings together biological and engineering approaches to fighting cancer. The Koch Institute will build on the pioneering work of MIT's Center for Cancer Research; the center's faculty members (along with 10 MIT engineering professors so far) have become its founding members. Koch's gift will also speed the construction of a new cancer research facility, which breaks ground this March and is scheduled to open in 2010.

"Bringing in folks from other disciplines is important in the fight against cancer," says Koch Institute director and biology professor Tyler Jacks, who directed the Center for Cancer Research. "We have the best engineers in the world, so our work force is unmatched."

Jacks says that viewing cancer as an engineering problem--a rela­tively new idea--promotes new approaches to basic research and new ways of tackling practical problems. On the basic-research front, it means applying the mind-set and tools of engineering: looking at cells as complex systems and harnessing computer models that can make sense of large amounts of data. On the applied side, it means developing new drugs, new materials for delivering drugs, and new devices for monitoring disease progression.

Many MIT cancer researchers had already adopted this approach in the last five years or so, says Jacks, and the influx of funding and institutional support will ensure that their projects flourish.

"There's an old-school artificiality to the idea of 'engineers' and 'biologists,' " says Dane Wittrup, a professor of chemical engineering and bioengineering and a member of the Koch Institute. To accomplish anything in the biomedical field, he says, engineers "have to have biology in their labs and in their brains."

Bhatia, who holds an MD in addition to her MIT degrees, agrees. Biologists and engineers have complementary skills; ideas flow in both directions, which is what makes working in both fields so exciting, she says: "We see many often unexpected examples of engineering enabling science through tool development, and science being translated through engineering into diagnostics and therapeutics."

Here are three projects at MIT that illustrate how melding engineering and biology could help researchers understand--and ultimately cure--cancer.

Bottling Evolution
Dane Wittrup is a protein engineer. He takes cancer therapies and tries to make them work better, with fewer side effects, through a combination of luck and design.

Wittrup makes high-performance antibody therapies that mobilize the immune system against cancer cells, which thrive because the body fails to recognize them as malignant. Classic chemo­therapy drugs are "poisons" with harsh side effects, he says. An antibody protein, on the other hand, generally has fewer side effects because it binds to one particular target, such as a tumor antigen. "The immune system sees that [a cell] has antibodies all over it and responds: 'It's coated with antibodies, so I'm gonna kill it,' " he says.

In order to make better-performing protein therapies, Wittrup uses what's called directed evolution. "You're bottling Darwinian evolution and setting the survival rules yourself," he says. First, he creates tens of millions of mutated versions of the gene for a particular protein and inserts each gene into a yeast cell. Then he uses various screening techniques to identify the yeast cells carrying the best version of the protein. This might be the protein that binds most strongly to a given target or the protein that's most stable in a particular range of temperatures, among many other possibilities. Wittrup says that protein engineers have refined directed evolution to the point that they can use it to make whatever proteins they want. Now, instead of just working on new tools for designing proteins, he uses such tools to make proteins that could help treat cancer.