When Bad Bugs Go Good

Like a seasoned burglar, the virus circles a human cell looking for the easiest point of entry. Within seconds, it has broken into its target, located the nucleus and deftly slipped its genetic material into the cell's DNA. Now whenever the cell divides to copy itself, it also makes copies of the interloper. Soon those multiplying viruses have hijacked not just that cell but also all its neighbors, turning them into one massive virus factory. When the cells can no longer make the proteins they need to survive, they start, one by one, to die.

And that's exactly what Dr. Stephen Russell was hoping for. A cancer specialist at the Mayo Clinic, Russell does everything he can to aid and abet those viral bandits. He arms them with detailed instructions for finding their target cells and outfits them with specially designed protein keys to speed up entry. As far as he's concerned, those viruses are the good guys, since the cells they are attacking and destroying are cancer cells in a fast-growing tumor.

In labs like this around the world, bad bugs are undergoing the ultimate rehabilitation, being transformed from life-threatening viruses and bacteria into lifesaving therapeutic agents. Using the tools of molecular biology, researchers like Russell are disguising and manipulating common microbes so that they will do good instead of harm. After all, nothing is better than a virus at evading the body's immune defenses and breaking into a cell. And nothing is better than a bacterium at producing deadly toxins that destroy a cell from the inside. "We can make a good anticancer agent," says Russell, "by harnessing and channeling these destructive powers."

The bad-bug--good-bug strategy was championed by doctors treating allergies and infectious diseases. The idea was to expose patients to small quantities of partly disabled microbes to jump-start their immune system. But cancer researchers have taken the approach one step further, turning microbes into tiny Trojan horses that can sneak into tumor cells and destroy them from within. "There is a good probability that microbe approaches will be part of the arsenal of the future," says Kenneth Kinzler, a cancer researcher at Johns Hopkins Hospital's Kimmel Cancer Center who is working with the clostridium bacterium. "We're betting on it."

Until quite recently, that wouldn't have been a smart bet. The idea of harnessing microbes to do a doctor's bidding flourished briefly in the 1960s, during the early days of the genetic revolution. Scientists sketched out grand plans for treating disease by adding or removing genes taken from bacteria or viruses. Because they were so good at penetrating cells, infectious agents seemed the ideal vehicles for delivering drugs. Some cancer patients were treated with experimentally modified viruses, and a few even saw their tumors shrink. Too often, however, scientists lost control of their microbial partners. "It wasn't possible at the time to engineer them to make them more specific," recalls Russell. "When they did work, there was a price to pay. The tumors were cured, but the patient died."