Has This Microbiologist Found the Answer to Antibiotic Resistance?

In anticipation of the upcoming fourth season of our HBO show which will premiere this February, we are releasing all of season three for free online. Watch all the episodes here, and don't miss the premiere of season four on Friday, February 5, at 11PM on HBO.

Last spring, for the third season of VICE on HBO, VICE correspondent Thomas Morton explored the very real possibility of a world without antibiotics, looking at the sometimes-perilous search for as-yet-unknown plants that might contain the keys to a new breed of bacteria-fighting drugs. Without new therapies, people are already starting to die from antibiotic-resistant "superbugs" like the dreaded MRSA infection, a deadly version of staph.

But microbiologist Michael Schmidt of the Medical University of South Carolina, thinks there may be a way to avoid this post-antibiotic crisis. According to Schmidt, conventional thinking about antibiotics has helped bring humans to this crisis point. It was inevitable that bacteria would adapt to dodge the effects of even the best antibiotics, since those antibiotics were essentially just chemicals produced by co-evolving organisms, or synthesized to mimic what those co-evolving organisms would produce.

"This arms race has been going on since the beginning of time," Schmidt said in an interview last week. "We've got about 30 more years of antibiotics left, [until] the microbes outsmart us. Unless we become clever."

According to Schmidt, this cleverness could involve plotting a new way to kill deadly bacteria. Specifically, Schmidt's research has focused on usingBacteriophages (or phages as they're informally known,) a category of naturally-occurring bacteria fighters that use a different strategy than typical antibiotics in the fight against bacteria.

Most antibiotic drugs work by finding various cell vulnerabilities in bacteria that do not exist in human cells. In contrast, a bacteriophage—basically a "bacteria eater"—is a virus that infects a bacterium. Like all viruses, bacteriophages are not lifeforms per se, just little packets of matter that attach to cells, and trick them into making more packets of matter, and on and on, ad nauseam. And they are astonishingly common—perhaps the single most common organic "entities" in the entire biosphere. They're everywhere: In the air, the ocean, the North Pole and even our bodies.

"They're out there, just floating as these inert objects, waiting to bump into a microbe," Schmidt told me. Any given bacterium likely has a whole army of phage that can target it. "The phage is the key, and it will find the lock," he explained.

That gives phages an edge in the fight against bacteria. Over the billions of years bacteria and phage have fought each other, bacteria have evolved to fend off one phage or another, but they haven't become phage-proof. What's more, bacteriophages absolutely can be used to kill infections—in fact, the first use of phage therapy to cure infections actually predates penicillin. Phages have just rarely been practical or reliable in medicine.

Schmidt tried to fix that problem a little over a decade ago. "We did research on taking advantage of the molecular syringe aspect of phage, and what we had them do is inject instructions for the microbe itself to kill itself," he told me. It worked extremely well. "Every mouse that got the phage was cured, and every mouse that didn't get the phage unfortunately succumbed to the infection," Schmidt said.

Unfortunately, he added, there are hurdles that still prevent phage therapy from being a silver bullet, even in a lab. First of all, not all phages can compete with the human immune system, which is always on the prowl for intruders. Bacteria can also bring a version of a phage with them when they infect a host, making the host "lysogenic"—in a sense, immune to the phage. "If you happen to be lysogenic to phage that you're using to treat that infection, the drug won't work," Schmidt said.

In 2003, Schmidt and his team developed a workaround for these problems, programming phages to carry a lethal set of instructions for bacteria. "We didn't actually make any phage. We just programmed [the bacteria] to die," he said. "We called it a lethal-agent delivery system."

According to Scmidt, lethal agents can even target MRSA, the scariest antibiotic-resistant superbug. The trouble isn't making these lethal agents—which Schmidt calls "magic bullets"—but getting them approved in pharmaceutical treatments. "With every bullet you create, it creates an FDA regulatory pathway" Schmidt said. "Quite frankly, that is the biggest hurdle to ethical phage therapy."

Some scientists are dismissive of Schmidt's approach to phage therapy, arguing that engineering phages is a waste of time and money, given that so many bacteriophages already exist in nature. But Schmidt thinks his lethally-armed phages could be ripe for a resurgence, thanks to improvements in the technology needed for large-scale manufacture.

"When we were starting this 15 years ago, it was a very different cost structure, but now in 2016, it's less expensive," he said. "It could become a viable option."

But Schmidt acknowledges that there are other ways to cure superbugs with phage therapy. In fact, to my astonishment, he told me that if I had, say, a child infected with MRSA, and I took it upon myself to find the cure, I could potentially find phages out in nature, and use them to "create a [phage] cocktail that would take out the MRSA."

The first step in this highly scientific process would be to fetch a bucket of sewage. "You'd isolate the MRSA from your child's wound, plate it on a petri plate, and then you would literally take drops of sewage, filter them out, and figure out which drop of sewage would wipe out the MRSA on the petri plate," Schmidt explained. "Then you could clean that up some more through dilution and purification, and make your own drug fairly quickly."

What he's describing, he said, is not unlike a technique for fighting local bacteria with local phages. The local phage method that has worked in trials in the former Soviet Union, where experimentation with phage therapy is still very active.

One way or another, if the antibiotic apocalypse comes, and we're all dying of seemingly incurable infections, phages could well come to our rescue. "It's not a question of knowing how to do it; it's a question of doing it," Schmidt said.

Follow Mike Pearl on Twitter.