At the same time Kim Lewis was decoding the mysteries of persister cells, he teamed up with Northeastern microbiology professor Slava Epstein to search for new antibiotics.
In 2001, the two men set out to solve a puzzle that has confounded scientists for more than a century: Why are scientists unable to grow 99 percent of the world’s microbes in a petri dish?
The question is far from academic. It means that scientists can use only 1 percent of the material on the planet that might lead to new medicines. With this severe limitation on raw material, it’s no surprise that the development of new antibiotics has slowed to a trickle in the past four decades.
For Lewis, it was another intriguing paradox: Why do these microbes flourish in the wild, but won’t grow in the most nutrient-rich laboratory medium?
“This seemed like a fascinating puzzle to solve,” says Lewis. “Slava and I did not focus on developing a better medium. A hundred years of failure suggested that that was not a good way to go.”
Instead, they looked for a way to simulate the wild environment while maintaining the controlled setting of the petri dish.
The result was the invention of the Cultursys diffusion chamber, which Lewis describes as “a relatively simple contraption” that makes it possible to grow microbe colonies in their natural environment while maintaining the control of a lab. It consists of two semipermeable membranes (think coffee filters) about the size of a beer coaster separated by an O-ring. A sample of soil containing the microbes is placed in the doughnut hole of the O-ring, and the membranes that seal the top and bottom allow chemicals (but not the cells themselves) to flow back and forth between the artificial and natural environments.
“The bacteria perceive it as their natural environment,” says Lewis. “They don’t know we tricked them, and as a result, everything grows.”
The next task was to identify those growth factors and begin testing the tens of thousands of previously ungrowable microbes to see which ones held the key to the next drugs.
In 2006, Northeastern received a patent for the Cultursys diffusion chamber while Lewis and Epstein formed a company, NovoBiotic Pharmaceuticals of Cambridge, Mass., to develop new antibiotics. So far, 25 have been isolated. Although most appear to be too toxic for human use, two look promising:
• Novo 25, which could replace penicillin, is in the advanced stages of development.
• Lassomycin, a potential treatment for antibiotic-resistant tuberculosis, is still in the test tube stage of development.