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    Friday, May 03, 2024

    Dodge Pond in East Lyme yields healing virus

    Dodge Pond in East Lyme is seen from the air in 2005. (Sean D. Elliot/The Day)
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    East Lyme — Small but deep, Dodge Pond sits tucked behind Town Hall in the center of Niantic village, all but hidden from view behind houses and thickets along its shore.

    But it has been very familiar to David Post since 2004, and is now becoming well known in the research labs of Yale University in New Haven, where he works, and beyond.

    Post, professor of ecology and evolutionary biology at Yale, has been regularly sampling and testing the waters of Dodge Pond and other nearby lakes as part of his research into aquatic food webs. Last year, he provided one of his Dodge Pond samples to a fellow Yale researcher involved in a needle-in-the-haystack kind of search. 

    And, of the more than 100 samples associate research scientist Benjamin Chan tested, the one Post gave him from Dodge Pond provided the miracle cure he was seeking.

    "It's exciting that a lake just down the road is the source of something used for medical treatment," Post said.

    Before the recent discovery, Dodge Pond was better known for the alewife that spawned there for centuries, and the Navy's sonar research there since the 1950s. A natural pond formed by glaciers, its connection to the sea through the Pattagansett River hasn’t been blocked by dams like many other waterways, so alewife still swim there to spawn every spring.

    Its 50-foot depth and suburban setting makes it the ideal spot for the Navy’s Undersea Warfare Center in Newport to test equipment. The testing lab is housed inside a windowless building atop the end of a long pier that extends over the 34-acre pond.

    “It’s the Navy’s most modern open water acoustic testing and evaluation site,” said John Woodhouse, spokesman for the warfare center. “The advantage of it is that it’s very quiet.”

    Along with the positive attributes, there is also the problem of mercury in the water. The state advises people not to eat fish caught in Dodge Pond because they contain the neurotoxin.

    State officials periodically have worked with the Navy to try to pinpoint the source of the contamination, according to Dennis Schain, spokesman for the state Department of Energy and Environment Protection, which has a public boat launch on the pond.

    Now though, Dodge Pond’s unique mix of distinctions are being eclipsed by an even more noteworthy feature. Its waters, it turns out, contain healing powers that may provide a solution to the growing problem of antibiotic-resistant infections.

    “I’m just so glad that the treatment worked,” said Chan, surrounded by vials and microscopes at Yale’s Osborn Memorial Lab, where he works. “I hope it can make a difference.”

    The intriguing tale of how a water sample from Dodge Pond healed a very sick man began early last year, four years after Dr. Ali Khodadoust first got a bacterial infection in his heart and chest cavity after surgery for an aortic aneurism. Khodadoust, an ophthalmologist who runs the Connecticut Eyecare Center in New Haven, spent months in the hospital getting heavy doses of antibiotics to treat the infection with a relatively common bacteria called Pseudomonas aeruginosa.

    “The bacteria was very persistent,” said Dr. Deepak Narrayan, professor of surgery at Yale Medical School, who treated Khodadoust at Yale New Haven Hospital. “There were abscesses and fistula that kept coming to the surface, and the bacteria became resistant to the antibiotics.”

    The infection became life-threatening. Surgery was deemed too risky.

    “This is where it gets almost bizarre,” Narrayan said. A coincidental meeting with Chan, the Yale associate research scientist, led Narrayan to the remedy for Khodadoust’s infection.

    In search of phages

    Attempts to reach Dr. Khodadoust, 80, were unsuccessful.

    An immigrant from Iran, he visited his home country several years ago to set up an eye hospital there, and this spring has returned there to work for an extended period, according to an assistant in his New Haven office. But he told his story to STAT, a Boston-based health and medicine publication, in its December issue.

    Narrayan and Chan call him an amazing man, one who cheated death at an advanced age and still has the drive to share his medical skills with his native country.

    “He’s fantastic,” said Chan, who met Khodadoust a few months ago when he visited the Osborn lab after the successful treatment.

    The treatment came from a unique virus Chan found in the water sample from Dodge Pond.

    Chan came to Yale in 2013 to research bacteriophages, which are a special kind of viruses that infect bacteria. He travels the world in search of phages, often going to the most undesirable places to find them — sewage treatment plants, dirty streams and polluted rivers.

    “This is a bunch of samples from the Middle East, Africa, Haiti, Mexico, Israel,” said Chan, opening a lab refrigerator filled with thin vials of water. “Every phage you isolate from these samples is new to science. I could sample from the same puddle in Haiti twice and I wouldn’t get the same phages.”

    The most numerous life form on the planet, phages are constantly changing and evolving in the presence of different bacteria. They have been known to science for more than a century, and were promoted as a possible means of treating bacterial infections.

    But with the subsequent development of antibiotics, researchers — at least in the West — lost interest in phages, Chan said.

    Interest never waned, though, in Eastern Europe and Russia, and today phage therapy is commonly used there. On a recent trip to Moscow, Chan said, he visited a pharmacy and bought four small vials of phages for $10 that were being sold as a remedy for gastrointestinal troubles.

    “In Russia and Georgia, they’ll put multiple phages together to treat an infection,” Chan said.

    In this country, phage therapy isn’t approved by the Food & Drug Administration, and pharmaceutical companies haven’t been motivated to seek FDA sanction — at least not yet.

    Over the years, Chan said, there have been a few “one-off” cases of successful phage therapy in this country, but no appetite to determine whether it could be applied on a large scale. Part of the problem is that phages are the unique byproducts of the nature around them, so none of them can be claimed by a company like Pfizer or Merck as their own.

    “There’s been a lack of commercial interest, because there’s no intellectual property people can get exclusive rights on,” Chan said. “It’s a difficult model for companies.”

    But with the growing problem of antibiotic resistance, that could change, Chan believes.

    'Match made in heaven'

    For Dr. Khodadoust’s treatment, Chan obtained a sample of the infecting bacteria from Dr. Narrayan. He cultivated it in his lab, and set to work introducing various phages from his collection.

    After a month of failures, he tried the phages from Dodge Pond and saw they were destroying the bacteria, and doing it in a novel way.

    The bacteria had become resistant to antibiotics by creating internal pumps to rid themselves of the killer chemicals. The phages from Dodge Pond attacked through those same pumps, killing the host bacteria. And the few surviving bacteria, Chan found, didn’t have the pumps, so the treatment could be followed up with antibiotics that would finish off the stragglers.

    “It’s almost like providing the burglar with the keys to the house,” Dr. Narrayan said of the phage’s strategy for attacking the bacteria. “It was like a match made in heaven.”

    He and Chan obtained FDA approval to use the treatment on Dr. Khodadoust under the agency’s compassionate emergency provision. Once they had the permission, Chan began cultivating the phages in his lab.

    “I cleaned it up here. I prepared 15 million viruses, and they injected 5 million into him,” Chan said. “The huge benefit of this treatment is that once the bacteria are gone, the phages break apart. They self-amplify and self-limit.”

    Both Narrayan and Chan say the case may have interesting implications for the future, but caution not to draw conclusions that are too sweeping.

    “This is just one case, one patient,” said Narrayan, who told the story of Dr. Khodadoust at a medical conference this past fall.

    Still, with antibiotic resistance proving ever more challenging, Chan believes phages hold great potential as a new weapon in the fight against infections. Working with Yale New Haven Hospital and Epibiome, a California-based biotechnology company, he is now seeking FDA approval for a clinical trial of phage therapy to treat antibiotic-resistant pneumonia.

    “It’s a big problem in people with cystic fibrosis,” Chan said.

    In pursuing phage research, Chan noted, he carries on a path set at Yale more than 100 years ago by Felix D’Herrelle, the researcher credited as the co-discover of phages and their possible use to treat infections.

    “If you look in the right places, phages are not hard to find,” Chan said. “There is a lot of potential, and there is growing interest in phages, because antibiotic resistance is such a common problem.”

    j.benson@theday.com

    Dr. Benjamin Chan, an assistant research scientist in ecology and evolutionary biology at Yale University, holds a tube containing a sample of a bacteriophage from Dodge Pond in East Lyme in his lab in New Haven Thursday, May 11, 2017. (Sean D. Elliot/The Day)
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    Dr. Benjamin Chan, an assistant research scientist in ecology and evolutionary biology at Yale University, holds a container with a growing sample, top left, of a bacteriophage from Dodge Pond in East Lyme in his lab in New Haven on Thursday, May 11, 2017. The Dodge Pond phage recently was used to save the life of a New Haven ophthalmologist suffering from a severe antibiotic-resistant infection in his chest. (Sean D. Elliot/The Day)
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