How genetically engineered viruses — and a rotten eggplant — prolonged a teenager’s life

How genetically engineered viruses — and a rotten eggplant — prolonged a teenager’s life

In 2010, an undergraduate in Durban, South Africa, found herself scraping muck from the underside of a partially decomposed eggplant. It was, in a sense, homework. She was taking a University of KwaZulu-Natal course on viruses that attack bacteria, and a semi-rotten vegetable seemed like a good place to find them. The “enriched soil sample,” she wrote, was dark and moist, wriggling with worms and other spineless lovers of decay.  The sludge proved lively on a microscopic level, too, and the student had soon picked out exactly what she was looking for: a never-before-described bacteriophage virus that kills certain mycobacteria. She named it Muddy and got on with her life, earning more degrees, landing a job at a communications agency. Muddy, meanwhile, landed in a lab freezer in Pittsburgh — one frost-filigreed tube among thousands.

But then, on Wednesday, a paper published in Nature Medicine pulled Muddy and two other viruses out of their frozen obscurity. These bacteriophages, the authors reported, beat back an antibiotic-resistant infection festering inside a 15-year-old in London. The patient wasn’t completely cured, but after more than six months of injections and topical treatments, she’d gone from bed-bound and tube-fed to school-attending and sushi-eating — a remarkable result given that some elements of her “phage therapy” had not previously been tested in humans.  Of the three viruses that helped, Muddy’s origin story is by far the most conventional. After all, scientists have plucked phages from the dirtiest places imaginable and used them as last-ditch therapies before, harnessing the viruses’ natural bacteria-bursting powers to save patients’ lives. The two other viruses, meanwhile, had to go through a kind of reverse domestication — converted, with genetic engineering, from relatively docile microbial parasites into efficient killers of infection.

“It is exciting. … This study is the first that we’re aware of using an engineered phage,” said Dave Ousterout, chief scientific officer of Locus Biosciences, a company not involved in the paper that is also working on enhancing the antibacterial capabilities of phages.  For months already, excited whispers about this news have been spreading, with cryptic hints dropped at conferences, rumors passed from biologist to biologist, academic to entrepreneur. “I kept hearing tidbits,” said Jessica Sacher, who runs a directory that connects clinicians and patients looking to try phage therapy as an experimental last resort with the microbiologists who keep collections of the viruses. “Some other researchers were saying, ‘Just wait, there’s going to be the first report of engineered phage in therapy soon.’” But as with all such case reports, the impressive details of how this work was accomplished — on top of the eggplant scraping, it involved a chance encounter in the Republic of Georgia, a close examination of some bird guano, and a loophole in British regulation of genetically modified organisms — make clinicians wonder to what extent the development can be scaled up to help combat the global crisis of antibiotic resistance.

“I still have real reservations about whether this kind of approach could be developed into something that could be usable on a large scale,” said Dr. Marcia Goldberg, an infectious disease specialist at Massachusetts General Hospital. “The amount of science that needs to go into developing a therapeutic against any single strain is huge.”


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