The Middletown Press (Middletown, CT)
Hunting for viruses that heal
Researchers study how phages treat infection when antibiotics can’t
NEW HAVEN — As antibiotics are becoming less and less effective at treating illnesses, the next weapon may be something old: viruses.
They’re not the viruses that make us sick, but viruses that attack and kill the bacteria that cause infections from MRSA to those that infect cystic fibrosis patients. Those viruses, called bacteriophages, or phages, have been used in Eastern Europe for decades, particularly in Georgia, Russia and Poland, but they never caught on in the West.
“Penicillin was discovered shortly after phages were discovered” said Ben Chan, an associate research scientist in the Yale University Department of Ecology and Evolutionary Biology. It was easier to use a broadspectrum antibiotic that killed most bacterial infections than to try to treat them with phages, each of which specifically targets one strain of bacteria.
The West’s overreliance on antibiotics, which has caused the bacteria to become resistant to so many — and in some people all known antibiotics — have made Eastern Europe’s wider use of phage therapy more attractive. Chan and Dr. Jon Koff, an internist at the Yale School of Medicine and director of the Adult Cystic Fibrosis Center, are leaders in the field.
Chan and Koff have used
phage therapy with 13 patients who have cystic fibrosis or noncystic fibrosis bronchiectasis, both of which make the patient vulnerable to bacterial infections. Those infections are one reason why cystic fibrosis patients have a life expectancy of less than 38 years.
BuzzFeed News reported last year that Chan had used phages on Paige Rogers, a Texas woman who has cystic fibrosis. The mucus that builds up in patients’ lungs is fertile soil for infection, in Rogers’ case Pseudomonas aeruginosa. By the time she turned 21, doctors told Rogers that no antibiotic was available to fight the bacteria that had evolved to resist every one.
The story of how Chan’s phages beat back the Pseudomonas bacteria and heal Rogers so that she could get back to a normal life is told in an episode of BuzzFeed’s Netflix series “Follow This.”
Chan is building a library of phages, about 1,000 so far, that can be called on to treat patients at Yale New Haven Hospital with antibioticresistant infections such as MRSA, a form of staphylococcus that is so prevalent patients can contract it in the hospital.
“I was involved because we had a patient in the medical intensivecare unit at Yale who was quite sick and was being seen by our infectious disease colleagues,” Koff said. “They asked Ben to help out with the clinical end of dosing,” such as deciding whether to use a nebulizer, which had been used with Rogers, or an intravenous drip.
Patients treated at Yale New Haven have come from Texas, Virginia, Vermont, New Jersey and Canada. All have been approved for “compassionate use” of phages because “there is no other treatment available to them, period,” Koff said. Since phages are not approved by the Food and Drug Administration for standard treatment, compassionate use approval must be sought, and the patients must be “willing to take the risk” that the virus won’t cause other problems, he said.
Chan said that after phage treatment, there will be a large drop in the number of bacteria after three days. The inflammation takes longer to heal.
Cures found in sewage
Chan left last week for Ghana, where he was on the hunt for phages in the stream of open sewage running through the capital of Accra. Phages are found everywhere — Chan writes on his web page that there are 10 million more phages than there are stars in the universe — but the best place to find them is where the sanitation is less than stellar.
Chan has been all over the world: to Mexico, Brazil and Paraguay, to Hong Kong and China, to Ethiopia, Rwanda, the Democratic Republic of Congo, Uganda and Haiti. Poor economies and high population density mean millions of phages. “It’s easier to collect a mix of untreated water in low and middleincome countries,” Chan said on the day his plane was taking off for Ghana.
Some of the phages Chan has collected can treat diseases that are not ordinarily found in the United States, such as cholera and dysentery. Others, however, will attack E. coli, which causes urinary tract and intestinal infections, salmonella and those that cause pneumonia or other lung infections.
Some phages will kill more than one bacterium. There’s an E. coli phage that also kills salmonella, Chan said, but most are specific to their target.
While there’s some luck involved, it’s not a totally random process to identify a phage that will kill a particular bacterium. When Chan collects a sample, he’ll find dead bacteria along with the phages, so he’ll know the phages’ targets.
In the hospital, “We get a sputum sample from the patient,” Koff said. “In the sample, we’re going to grow out the bacteria that’s there. You basically give the phage to that bacteria in a lab. If the phage kills the bacteria, then we know that that phage is going to be effective.”
Lowering antibiotic resistance
Some of Koff ’s 13 patients have had multiple phage treatments. The goal is for the phage to either kill the bacteria causing the infection or render it once again vulnerable to antibiotics. If the bug becomes resistant to the phage, that means it’s no longer resistant to antibiotics.
“It opens up the ability to use these antibiotics the bacteria become resistant to, number one,” Koff said. “Number two, we kill a lot of bacteria. It gives the immune system the ability to fight the infection.” Finally, the bacteria that remain are less inflammatory, he said.
Koff and Chan are planning to begin a clinical study on a Pseudomonaskilling phage that may start early next year. There are companies looking into making phage therapy commercially viable, including Locus Biosciences, Adaptive Phage Therapeutics, Armata Pharmaceuticals and Felix Biotechnology, which Chan cofounded with Yale professor Paul Turner.
In order to avoid conflicts of interest, Chan has no equity stake in Felix, named for a codiscoverer of bacteriophages, Félix d’Herelle, a FrenchCanadian microbiologist who taught at Yale.