When Bad Bugs Go Good

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Meanwhile, scientists at Vion Pharmaceuticals in New Haven, Conn., have been experimenting with another bacterium, salmonella, and another way of destroying a tumor from the inside out. Salmonella is a familiar but unwelcome interloper in kitchens and at picnics, thriving in uncooked meats and other food products such as eggs. Once in the blood, its surface coat can trigger septic shock, a hyperaggressive immune response that can lead to liver and kidney failure and a dangerous drop in blood pressure. Confined to a tumor, however, the bacterium could be a potent cancer killer. Like the measles virus, salmonella zeroes in naturally on tumor cells. "If an animal has a tumor, that tumor is salmonella's favorite place to go," says David Bermudes, director of microbiology at Vion. With a simple change in the bacterium's genome, the Vion team and Yale scientists were able to give salmonella the ability to convert a powerful compound found naturally in the body into a toxic chemotherapy agent. In a small pilot study conducted at the Mary Crowley Medical Research Center in Dallas, 2 of 3 patients given the modified salmonella showed signs that the chemotherapy agent was active. "It's a proof of principle that the strategy is working," says Bermudes. While his team seeks a partner to continue these studies, Vion is sufficiently convinced of the promise of bacteria-based therapies that it holds patents on potential cancer treatments from three more bacteria: listeria, streptococcus and shigella.

We may need all those microbes if the bad-bug approach turns out to be as successful as early trials suggest. Like AIDS cocktails and cancer chemotherapies, microbe-based therapies may require a multidrug approach. For example, combining the modified clostridium bacterium, which attacks a tumor at its anaerobic core, with the altered measles virus, which destroys the periphery of the tumor, could be a potent new way to fight cancer. Add some radiation or chemotherapy to mop up any lingering cancer cells, and doctors could find themselves closing in on a cure.