Merrikh, meanwhile, is focused on the antibiotic problem. “If you look at the history of antibiotics, in every single case, as soon as the drug hits the market, resistance arises. So the strategy of making new drugs isn’t ever going to work,” she says. “Our idea is that before the next drug hits the market, let’s have an anti-evolution drug to give alongside it, to at least delay the development of resistance.”
“All steps forward are good, and I think this is a great one,” says Michael Johnson from the University of Arizona. The challenge, he says, is to find a fast and efficient way of screening libraries of chemicals for drugs that can actually disable Mfd in the body of a human patient. Merrikh’s team is already on the case.
But wouldn’t bacteria eventually evolve resistance to the anti-Mfd drugs? “The chances are very low,” Merrikh says. “You’re turning off the mechanism that would do that in the first place.”
“I’m skeptical,” says Tara Smith from Kent State University. She has heard claims about evolution-proof drugs before, and they almost always fizzle out. Some scientists argued that bacteria were unlikely to evolve resistance to small molecules called antimicrobial peptides, because they were so diverse. One even put a bet on it—and lost. Others suggested that bacteria were unlikely to evolve resistance to viruses called phages, and were repeatedly proven wrong.
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Still, Smith says that Merrikh’s claims are “much more measured” than those from other researchers who have forgotten Orgel’s Second Rule. And “it’s one of those outside-the-box ideas that we need because, clearly, the usual model of antibiotic discovery, approval, use, and resistance isn’t working,” she says.
Many other scientists are also trying to find anti-evolution drugs. For example, Rahul Kohli from the University of Pennsylvania, is trying to disable the appropriately named “SOS response”—a system that bacteria use to cope with stress, and that also increases their mutation rates. His team has already identified drugs that can block that system.
The problem with disabling the SOS system, Merrikh says, is that bacteria become “very, very sick,” even in the absence of antibiotics. That creates an enormous incentive to evolve some kind of countermeasure. And that’s not the case with Mfd. When her team deleted it, the bacteria were nigh-indistinguishable from normal cells. That should reduce the impetus for bacteria to evolve their way around the hypothetical anti-evolution drug.
It might also be difficult to convince agencies like the FDA to approve anti-evolution drugs. It’s easy enough to prove that a drug can kill bacteria in a clinical trial, “but if you have a drug that prevents the development of resistance, going through clinical trials is going to be harder,” Merrikh says. “The effect is only going to be apparent in a population over many years. How to get a drug like that into the market is a big challenge.”