A fascination with the “first germ”
It may be notorious now as a murder weapon and potential agent of biological warfare, but when Philip Hanna was beginning his career, advisors tried to steer him away from studying something as unimportant as anthrax.
“It was considered a veterinary disease, not a human health problem, and its potential for biological warfare was not yet a publicly recognized issue,” Hanna recalls. Fascinated with the disease’s historical significance, he ignored the advice.
“Anthrax was the world’s first germ—proven by science, at least,” says Hanna. “At the advent of modern microbiology, anthrax was what scientists Robert Koch and Louis Pasteur used to prove that germs cause disease. I was attracted to the idea of being involved in a line of research that has brought so much good to so many people.”
Hanna saw Bacillus anthracis, the bacterium that causes anthrax, as a workhorse of a microbe that could be harnessed to gain broad insights into how bacteria cause disease. In lab animals, as in humans, the disease progresses quickly, “so you can study the course of infection in a work week,” says Hanna. And because of parallels to other infectious diseases, anthrax is a useful model for understanding diseases that are more difficult to study in the lab.
Bacillus anthracis is a bug designed for survival. It spends much of its life as a soil-dwelling spore that shows no signs of life and is remarkably tolerant of heat, sunlight, drought and even many disinfectants. In soil, spores can remain dormant for hundreds or thousands of years, but once they enter the body—through cuts or scrapes in the skin or by inhalation or ingestion—they somehow sense it’s time to move on with their lives, and they germinate into active forms that multiply like mad. Anthrax contracted through the skin is usually curable, but infections that result from inhaling or ingesting the spores can cause death with a day after symptoms begin. And because initial symptoms are vague and flu-like, treatment often comes too late.
Hanna’s main interest is in the early stages of infection. By closely examining each step, he hopes to find “choke points” where medical intervention might be most effective.
“When spores come into the lungs through inhalation, they don’t actually germinate in there; they’re taken up by white blood cells and transported to the lymph nodes around the heart and lungs,” says Hanna. “It’s during that taxicab ride to the inner recesses of the body that they recognize signals from the host that tell the spores they’re in the right place to germinate.” Once they arrive at their destination, the spores germinate and the active forms of the bacteria enter the bloodstream and start pumping out toxins.
“Our goal as biologists is to use the technologies of bioinformatics, proteomics, genomics and molecular genetics—which have become quite strong in the last 10 years—to find out what genes are expressed and what proteins are made at each step, whether they are required for that step and whether they make reasonable targets for new vaccines or antibiotics,” Hanna says.
Recent events that have focused attention on anthrax as a lethal weapon anger the researcher who was drawn to its potential for helping mankind.
“My lab group is motivated to work very hard,” Hanna says, “to do something to counter that threat.”