Skeptics have also argued that even if scientists could design an effective phage therapy, evolution
would soon render it useless. In the 1940s, the microbiologists Salvador Luria and Max Delbruck
observed phage resistance evolving before their own eyes. When they laced a dish of E. coli with
phages, most of the bacteria died, but a few clung to existence and then later multiplied into new
colonies. Further 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 to kill. 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.