Breakthrough method in cancer detection

by Rachel Mahan, BS '06 biological sciences, BA '06 English

Imagine you're oozing about on a gelatin-like substance, minding your business, when viruses begin emerging from your body! Congratulations, you're a bacterium, and the prognosis isn't good: You've got a viral infection, and your ability to reproduce is being exploited for a new technology.

Although not beneficial for the bacterium, this first stage in a relatively new molecular biology technology called "phage display" has huge potential health benefits for humans. ("Phage" is another name for a virus that infects bacteria, and scientists are interested in the foreign proteins they "display" on their outer coats.) In the future, phage display methods may be used for earlier cancer detection, among myriad other applications.

Curators Professor of Biological Sciences George Smith developed phage display technology, which he claims is "just simple microbiology," by building on his background in immunology. "I just happened to be in the right place at the right time," he says.

Smith may be modest, but John David, director of the Division of Biological Sciences, is ready with praise. He says Smith has been involved in multiple breakthroughs, and that "most of us (scientists) would be thrilled to be associated with one."

For his phage display technology, Smith won the 2007 Promega Biotechnology Research Award from the American Society for Microbiology.

Judy Wall, MU biochemistry professor and a member of the society, nominated Smith for the award. "On a scale of one to ten," she writes, "with 10 being a Nobel Prize, and becoming a National Academy of Sciences member being an eight, this would be about a six and a half to seven." She continues, "Few of us ever make an impact with new technologies."

Phage display technology, Smith says, is basically like fishing. To hook the viruses with protein coats of interest, scientists use bait (or another protein anchored to the bottom of a dish) to sort through an entire sea of viruses with different protein coats that wash over the dish. In other words, they use a protein to catch a protein.
A catch is made when the protein on a virus coat attaches tightly to the protein bait anchored to the dish. After the other viruses are washed away, the caught viruses are released and collected by researchers. Because virus protein coats are all different, only those with patterns of amino acid building blocks suitable for binding to the anchored protein will be caught.

Viruses, whether human or bacterial, aren't alive. They exist simply as a piece of DNA or RNA covered in protein. Because they can't even reproduce, viruses hijack the copying machinery that a bacterium uses to make copies of itself; thus, the viruses get copied.

Utilizing this ability, scientists infect bacteria with the viruses they catch. The bacteria then make many copies of the virus and its protein coat so the scientists don't have to. The virus is then no longer needed because scientists are interested only in its protein coat.

Smith's phage display work focuses on cancer detection. Researchers currently detect cancer by imaging all structures in the body and searching for abnormalities indicative of cancer. Usually, only relatively late-stage cancers can be detected.

But Smith and colleagues use phage display for "molecular imaging," a new approach to cancer detection that specifically images tumors, so even small, early tumors can be detected.

In addition to catching tumors before they spread, molecular imaging can enhance cancer therapy by allowing doctors to follow the progress of treatment. Numerous other practical applications in labs worldwide involve phage display, including therapeutic drug discovery, creation of synthetic vaccines, construction of wires for miniature circuits and detection of biological- and chemical-threat agents.

By using what he calls "simple microbiology," Smith has created a new technique that is changing the face of medicine and technology.

Links:

George Smith lab
Division of Biological Sciences