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research revealed that those survivors had acquired mutations that allowed them to resist the phages. The resistant bacteria then passed on their mutated genes to their descendants. Critics have argued that phage therapy would also foster the evolution of phage-resistant bacteria, allowing infections to rebound.
     
    The advocates for phage therapy respond by pointing out that phages can evolve, too. As they replicate, they sometimes pick up mutations, and some of those mutations can give them new avenues for infecting resistant bacteria. Scientists can even help phages improve their attacks. They can search through collections of thousands of different phages to find the best weapon for any particular infection, for example. They can even tinker with phage DNA to create phages that can kill in new ways.
     
    In 2008, James Collins, a biologist at Boston University, and Tim Lu of MIT published details of the first phage engineered tokill. Their new phage is especially effective because it’s tailored to attack the rubbery sheets that bacteria embed themselves in, known as biofilms. Biofilm can foil antibiotics and phages alike, because they can’t penetrate the tough goo and reach the bacteria inside. Collins and Lu searched through the scientific literature for a gene that might make phages better able to destroy biofilms. Bacteria themselves carry enzymes that they use to loosen up biofilms when it’s time for them to break free and float away to colonize new habitats. So Collins and Lu synthesized a gene for one of these biofilm-dissolving enzymes and inserted it into a phage. They then tweaked the phage’s DNA so that it would produce lots of the enzyme as soon as it entered a host microbe. When they unleashed it on biofilms of E . coli , the phages penetrated the microbes on the top of the biofilms and forced them to make both new phages and new enzymes. The infected microbes burst open, releasing enzymes that sliced open deeper layers of the biofilms, which the phages could infect. The engineered phages can wipe 99.997 percent of the E . coli in a biofilm, a kill rate that’s about a hundred times better than ordinary phages.
     
    While Collins and other scientists discover how to make phages even more effective, antibiotics are now losing their luster. Doctors are grappling with a growing number of bacteria that have evolved resistance to most of the antibiotics available today. Sometimes doctors have to rely on expensive, last-resort drugs that come with harsh side effects. And there’s every reason to expect that bacteria will evolve to resist last-resort antibiotics as well. Scientists are scrambling to develop new antibiotics, but it can take over a decade to get a new drug from the lab to the marketplace. It may be hard to imagine a world before antibiotics, but now we must imagine a world where antibiotics are not the only weapon we use against bacteria. And now, ninety years after Herelle first encountered bacteriophages, these viruses may finally be ready to become a part of modern medicine.
     

 

The Infected Ocean
     
    Marine Phages
     
    Some great discoveries seem at first like terrible mistakes.
     
    In 1986 a graduate student at the State University of New York at Stony Brook named Lita Proctor decided to see how many viruses there are in seawater. At the time, the general consensus was that there were hardly any. The few researchers who had bothered to look for viruses in the ocean had generally found only a scarce supply. Most experts believed that the majority of the viruses they did find in sea water had actually come from sewage and other sources on land.
     

    But over the years, a handful of scientists had gathered evidence that didn’t fit neatly into the consensus. A marine biologist named John Sieburth had published a photograph of a marine bacterium erupting with new viruses, for example. Proctor decided it was time to launch a systematic search. She traveled to the Caribbean and to the