The Drugs Start Here

If you were to develop one of the highly drug-resistant strains of tuberculosis, your survival might come down to a dose of capreomycin. For doctors trying to fight these newly emerging strains—the most dangerous form of the common bacterial infection—this antibiotic is a drug of last resort. If it doesn’t work, the fight is essentially done. “It doesn’t matter what you give them after that,” says CALS bacteriologist Michael Thomas. “You can’t treat them.”

While much of the planet is already facing a TB epidemic—2 million people died from the disease last year and as many as 2 billion are carriers—things could be much worse without capreomycin. It is deemed so valuable that it is listed as one of the planet’s essential medicines by the World Health Organization. Because bacteria evolve resistance to the weapons we throw at them, doctors are being urged to use capreomycin sparingly to preserve its killing power until something better comes along.

But new antibiotics rarely come along. During the past 38 years, only two truly novel antibiotics have been discovered, and pharmaceutical companies have largely backed away from the business of tweaking existing antibiotics to enhance their power. Capreomycin, for instance, was discovered in 1956.

Our bacterial foes have evolved while the drugs to fight them mostly haven’t.

The lack of activity on antibiotics is partly due to the early success of those drugs. They worked so well—and everyone assumed they’d continue working ad infinitum—that many large pharmaceutical companies dropped their antibiotics discovery programs. By the time drug resistance became a recognized problem, it no longer made sense to restart them. “It costs an obscene amount of money to develop a drug now,” explains Thomas. “And there just isn’t enough money (to be made in antibiotics) because when you take an antibiotic you get cured.” Drug companies prefer the profit potential of medicines for chronic conditions such as high cholesterol, where patients may spend years or decades on a medication.

Pharma’s disinterest has created a potentially explosive situation where our bacterial foes have evolved while the drugs to fight them mostly haven’t. In microbiology circles, people are saying there will be 15 untreatable infections within the next 25 years if things don’t change quickly. “Sometimes I feel like I’m being a doom-and-gloom, Chicken Little type,” says Jo Handelsman PhD’84, chair of the bacteriology department. But the talk she’s hearing lately tells her “it’s even scarier than I say it is.”

But the urgency has brought on a paradigm shift within the research community. Scientists who for decades devoted themselves to basic research have shifted gears to discover new antibiotics and improve existing ones. And they’re getting support from agencies such as the federal National Institutes of Health, which has embraced the notion that academics can help bring the next generation of antimicrobials to market.

“A few years ago if I had said, ‘I want to make new drugs in my academic lab,’ the NIH would have responded, ‘That’s not the kind of work we fund,’” says Thomas. “Now they are taking it very seriously, supporting the type of research that discovers new anti-infectives, because they know there’s this gap now.”