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Speaker 1: As infections become harder to treat because of antibiotic resistance,

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Speaker 1: scientists are enlisting help from bacteria's oldest enemy, viruses, so

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Speaker 1: called bacteria phases literally, bacteria eaters are viruses that target bacteria.

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Speaker 1: While researchers have known about them for a century and

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Speaker 1: even use them to treat people, these biological agents have

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Speaker 1: been largely ignored in most of the world since penicillin

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Speaker 1: became available until recently. That is Welcome to Prognosis, a

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Speaker 1: podcast about health and science, medical technology, and the changes

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Speaker 1: that are underway across the world. I'm your host, Michelle

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Speaker 1: fay Cortes. For our third season, we're delving deeply into

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Speaker 1: the human cost of bacterial infections that can't be stopped

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Speaker 1: by even our most potent antibiotics. The loss of these

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Speaker 1: miracle cures has been described as one of the biggest

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Speaker 1: threats to global public health. It spurred a search for

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Speaker 1: alternatives to antibiotics. In this episode, Bloomberg's Jason Gale explores

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Speaker 1: how that effort is leading scientists back to a Soviet

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Speaker 1: era inspired treatment known as phage therapy that's saving the

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Speaker 1: lives of patients who couldn't be cured with antibiotics alone.

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Speaker 1: He also examines the discoveries being made in some of

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Speaker 1: England's smelliest soils that promised to protect us against two

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Speaker 1: major sources of deadly disease. Here's Jason. This is Joe Grimwood.

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Speaker 1: He's a retired chiropractor who lives at the end of

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Speaker 1: a dirt road in the hills outside of Reno, Nevada,

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Speaker 1: with Jasmine, his fifty pound bulldog. People terry across and

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Speaker 1: more recently an orange second hand track and it's got

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Speaker 1: a loader bucket on the front and a scraper on

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Speaker 1: the back. It's what they call him midside. So it's

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Speaker 1: thirty five horsepower, three cylinder diesel. It's four wheel drive.

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Speaker 1: It could lift about eighteen hundred pounds. Joel has big

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Speaker 1: plans for it. So we're gonna redo the driveway here

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Speaker 1: with it. Well, what I want to do is put

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Speaker 1: a garden in over here, and it's you know, at

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Speaker 1: least a core acre. Joel is sixty six. He wasn't

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Speaker 1: always this active. In fact, a year and a half

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Speaker 1: ago he was gravely ill. I practiced chiropractic for over

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Speaker 1: twenty years on the north shore Lake Tahoe. In two

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Speaker 1: thousand and seven, I had a cardiac arrest and that

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Speaker 1: ended that Joel had a diseased hot muscle that put

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Speaker 1: him in cardiac failure. Five years ago. He became so

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Speaker 1: ill that he needed a hot transplant to buy him

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Speaker 1: some time while he waited for a donut. Ogan his

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Speaker 1: ductors implying to the mechanical pump known as a left

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Speaker 1: ventricular assist device, which is a pump that takes over

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Speaker 1: for your left ventricle and pumps blood from your left

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Speaker 1: ventricle to your order. The device fitted in Joel's chest

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Speaker 1: was powered by an electrical cord that exited his abdomen,

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Speaker 1: and this cord it was a direct connection between the

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Speaker 1: inside of his heart and the outside world. Despite his

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Speaker 1: best efforts to keep it clean, bacteria started growing inside

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Speaker 1: the pump. Within a year, Joel was battling a potentially

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Speaker 1: deadly infection. I was in all the hospital for three years.

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Speaker 1: I was on ivy antibiotics most of that time, and

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Speaker 1: they just never could quite knock it out. Surgeons would

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Speaker 1: scrape away dead tissue, vacuum up bacteria laden material, and

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Speaker 1: sterilize and dress an open wound that gradually grew to

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Speaker 1: the size of a key line in Joel's case. Antibiotics

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Speaker 1: were subduing the jams in his bloodstream, but we're powerless

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Speaker 1: against their mushrooming source, the slime forming bacteria growing on

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Speaker 1: his implant. Scientists called the slime bio film. As a

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Speaker 1: survival strategy, Bacteria builds structured communities on surfaces, including on

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Speaker 1: artificial hips and knees, pacemakers, and catheters, even on airways

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Speaker 1: of cystic fibrosis patients. This gunk is a fortress light

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Speaker 1: barrier that protects bacteria from antibiotics and the immune system.

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Speaker 1: The propensity for bacteria to develop bio films and prosthetic

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Speaker 1: implants is a major threat to modern medicine. For instance,

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Speaker 1: more than a million knee and hip replacement operations are

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Speaker 1: performed annually in the United States alone, and the joint

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Speaker 1: infections that result cost more than one billion dollars in

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Speaker 1: hospital bills. You know, I was in trouble and I

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Speaker 1: is going to die. I was getting out feeling, but

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Speaker 1: I never lost the whole, the faith of belief that

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Speaker 1: I had survived this. I don't think there was much

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Speaker 1: point in thinking any other way. I had to stay positive.

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Speaker 1: Joel sent me pictures of what his chest looked like

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Speaker 1: without the dressings. His gaping chest wound is about six

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Speaker 1: inches long and the color of uncooked steak. I'm not

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Speaker 1: especially squeamish, but being able to see directly into his

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Speaker 1: body and identify the mushroom shaped base of the pump, well,

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Speaker 1: it made me feel nauseous. Joel desperately needed a new heart,

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Speaker 1: but the bacterial slime growing on his heart pump made

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Speaker 1: a transplant too dangerous. Four hospitals refused to put him

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Speaker 1: on the waitlist because of the infection risk. Removing the

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Speaker 1: device would dislodge a lethal maelstrom of staff Loococcus aureous bacteria.

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Speaker 1: If Joel was going to survive, he needed to get

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Speaker 1: rid of the bacteria, and that was impossible with antibiotics alone.

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Speaker 1: And the last I'd say six months or so, I

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Speaker 1: really got a sense of urgency because it just wasn't

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Speaker 1: going away. Hope was dwindling. That is until the fifth

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Speaker 1: hospital offered John something Else, a type of experimental treatment

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Speaker 1: that had been courageously attempted there a couple of years earlier.

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Speaker 1: It was subsequently tried with overall positive results in half

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Speaker 1: a dozen patients in much of two thousand and six,

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Speaker 1: Californian academic Tom Patterson became the hospital's first recipient. He

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Speaker 1: got severely ill with an incurable bacterial infection. He was

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Speaker 1: close to dying in the hospital attached to the University

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Speaker 1: of California, San Diego, when his wife came up with

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Speaker 1: one last option, an approach that flourished in the former

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Speaker 1: Soviet Union under Stalinism but hadn't been used in the

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Speaker 1: US for generations. And that's page therapy. This is Stephanie Strafty.

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Speaker 1: I'm an infectious disease epidemiologist and the Associate Dean of

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Speaker 1: Global Health Sciences at UC San Diego, where I also

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Speaker 1: co direct a new feage therapy center called iPath. The

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Speaker 1: treatment involves using specially selected and prepared viruses to attack

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Speaker 1: disease causing bacteria. Professor Strafty took that unconventional approach to

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Speaker 1: save her husband Tom, and its success led to Joe

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Speaker 1: Grimwood and other patients getting it. In Tom Patterson's case,

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Speaker 1: it was a last ditch attempt to keep him alive.

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Speaker 1: He had already had seven cases of septic shock, and

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Speaker 1: so it was either watch him die or do something

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Speaker 1: drastic on my own and I decided to try to

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Speaker 1: save his life. Professor Strafty didn't set out to become

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Speaker 1: an expert in phage therapy. In fact, she devoted decades

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Speaker 1: focusing on the HIV epidemic that got derailed somewhat into

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Speaker 1: In sixteen, my husband and I were on vacation in

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Speaker 1: Egypt and he acquired what looked like to be a

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Speaker 1: stomach bug, but he got violently ill. He was eventually

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Speaker 1: met a back to Germany and then back home to

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Speaker 1: UC San Diego, where our doctor friends were caring for him,

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Speaker 1: and it turned out that he had a gall stone

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Speaker 1: that caused a giant abscess in his abdomen, and inside

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Speaker 1: that abscess lurked a superbug. The infection was caused by

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Speaker 1: a bacterium called a senator. Back to Baumannii, it possessed

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Speaker 1: so many drug resistance genes that it was untreatable. Professor

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Speaker 1: Stratti says she stopped counting the number of antibodics was given.

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Speaker 1: His infection was resistant to fifteen antibiotics right off the bat,

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Speaker 1: and it was only partially sensitive to three, and in

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Speaker 1: the few weeks that it took to um get him

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Speaker 1: back home to San Diego, it acquired resistance to those

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Speaker 1: last three antibiotics, including Calliston and mirror pennum, and those

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Speaker 1: are considered last resort antibiotics. The bacteria is nicknamed Araqua

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Speaker 1: BacT because of the veterans you have returned from the

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Speaker 1: Middle East with the infection. This is an organism I

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Speaker 1: used to play on my petri dishes back in the

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Speaker 1: nineteen eighties at the University of Toronto, and it was

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Speaker 1: considered a pretty wimpy organism back then. But it's acquired

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Speaker 1: superpowers at the bacterial level because it's almost like a kleptomaniac.

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Speaker 1: It steals antibiotic resistance genes from other bacteria, and when

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Speaker 1: we're throwing antibiotics at an infection, this one is resistant

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Speaker 1: and it's just rubbing its hands together saying, okay, you

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Speaker 1: got rid of my competition. Now I can move in

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Speaker 1: for the kill and a head Professors straths husband Tom

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Speaker 1: firmly in its clutches. He was possibly ours away from death.

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Speaker 1: His doctors had given us the talk. They said, basically,

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Speaker 1: there's nothing else that we can do. This organism is

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Speaker 1: resistant to all antibiotics. Desperate, Professor Strathty clung to something

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Speaker 1: she recalled from her undergrad days back in Canada. Well,

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Speaker 1: I have a very old degree in microbiology from the

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Speaker 1: nineteen eighties, and I had learned in my classes that

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Speaker 1: pages are viruses that have naturally evolved to attack bacteria,

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Speaker 1: and you can see how they work in a petri dish,

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Speaker 1: even though you can't visualize them with your naked eye

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Speaker 1: or even with a light microscope. But what I didn't

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Speaker 1: know is that pages had been used over a hundred

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Speaker 1: years ago to treat people with bacterial infections quite successfully.

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Speaker 1: For a time, Professor Strathty worked with scientists in Texas

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Speaker 1: and the US military to acquire cocktails of pages that

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Speaker 1: matched the bacteria poisoning her husband. Meantime, she worked with

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Speaker 1: his doctors and the Food and Drug Administration to gain

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Speaker 1: approval to use them on compassionate grounds. The first batch

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Speaker 1: arrived from Texas A and M University, and we inserted

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Speaker 1: those into the tubes or catheters in his abdomen because

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Speaker 1: that was closest to his infection, and we just hoped

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Speaker 1: that nothing would happen, because you know, we were worried

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Speaker 1: that he could die of septic shock because essentially we

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Speaker 1: were injecting a billion viruses into his body and he

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Speaker 1: remained stable. So two days later we had phages arrived

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Speaker 1: from the Navy, and those pages were considered to be

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Speaker 1: more virulent. We injected those pages into his body, a

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Speaker 1: billion pages per dose, and that was when he really

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Speaker 1: started turning around. While it's impossible to prove that it

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Speaker 1: was phage therapy that saved Tom's life, what happened next

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Speaker 1: was dramatic. A couple of days after we began intervene

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Speaker 1: his phage therapy, he lifted his head off the pillow

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Speaker 1: and kissed his daughter's hand, and everybody in the icy

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Speaker 1: freaked out, including myself. Doctors observed something very cool in

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Speaker 1: Tom's case. The bacteria had to make a genetic decision.

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Speaker 1: It could either face the phage or it could face

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Speaker 1: anti bio artic and it decided to face the antibiotic,

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Speaker 1: so it actually modified itself to become susceptible to antibiotics. Again,

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Speaker 1: this synergy between phages and antibiotics has occurred in other patients.

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Speaker 1: After phage therapy, their superbug was no longer immune to antibiotics,

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Speaker 1: and it's opened up a way of resurrecting failing antibiotic regimens.

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Speaker 1: If we can take advantage of the fact that features

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Speaker 1: can put selective pressure iron bacteria to make them susceptible

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Speaker 1: to some antibiotics. Again, then that would be a really

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Speaker 1: important advance. Even if it saves just a couple, that

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Speaker 1: could be a very important turning point in this whole

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Speaker 1: global crisis that we're facing. In the case of Joel Grimwood,

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Speaker 1: whose chest was being slowly consumed by bacterial slime, pages

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Speaker 1: are credited with doing something else as equally cool. After

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Speaker 1: a four week course of intravenous phage therapy in combination

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Speaker 1: with antibiotics, swabs of his open wounds came back negative.

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Speaker 1: For staff, it was like it ate the bacteria and

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Speaker 1: then when all the bacteria was gone, it just went away.

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Speaker 1: It just died. But once I started taking the phage,

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Speaker 1: there was a marked improvement in my energy level and

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Speaker 1: how I felt. I'd say within a week I started

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Speaker 1: to notice differences. Importantly. After four years, some forty surgeries

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Speaker 1: and a multitude of medical treatments, he was finally eligible

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Speaker 1: for heart transplant surgery. Doctors chalked up his surprising turnaround

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Speaker 1: to phage therapy. They qualified me for the transplant, and

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Speaker 1: in two weeks I got a heart. Joel Grimwood and

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Speaker 1: Tom Patterson epitomized the dramatic results that have revived interest

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Speaker 1: in phage therapy to counter untreatable infections. But the basic

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Speaker 1: research required to find and developed phage based products that's

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Speaker 1: off and frustrating and well sometimes downright gross work. It

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Speaker 1: involves getting up close and personal with some large sources

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Speaker 1: of bacteria. What we can see here are some really healthy,

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Speaker 1: lovely picks. I think they're I think they've lost our

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Speaker 1: old spots. This one with the spots. That's Martha Clokey.

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Speaker 1: She's a micro biologist who runs a research lab and

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Speaker 1: teaches at the University of Leicester, roughly a hundred miles

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Speaker 1: north of London. She's responsible for some key phage findings

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Speaker 1: that promised to not only improve food safety, but to

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Speaker 1: rest a major killer of hospital patients. On an overcast

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Speaker 1: summer's day, Professor Clokey is at a farm in East Lake,

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Speaker 1: The swine are huge, one bore probably waist close to

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Speaker 1: five hundred pounds. But Professor Cloaky isn't here to just

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Speaker 1: visit a farm she's hunting pages. It's not what's in

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Speaker 1: the pigs that interests her, it's what's beneath them. It's

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Speaker 1: a microbial treasure trove comprising soil and pig excrement. We

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Speaker 1: get virus like Fluvola eight bacteria of their own viruses

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Speaker 1: known as pages. So that's what all our works about,

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Speaker 1: is trying to find these very specific bacterial viruses that

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Speaker 1: we can then used to treat diseases and animals and humans.

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Speaker 1: A quarter of a teaspoon of this smelly stuff will

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Speaker 1: harbor tens of billions of bacteria and hundreds of billions

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Speaker 1: of pages, which is why farm soils are fertile ground

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Speaker 1: for Professor Cloak. So it's a wonderful, natural, lovely microbial

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Speaker 1: soupt of bacteria feeding on the on the soil, playing

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Speaker 1: all different roles, living off the nutrients, some of which

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Speaker 1: are provided by the animals, which is why we often

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Speaker 1: findvirus is a target different bacteria the animals carry. So

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Speaker 1: it's in order to find good features, we start off

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Speaker 1: with a source of healthy animals and we search through

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Speaker 1: the soils and feces associated with them, such as this

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Speaker 1: sample here. It's immaterial like this that Professor Cloaking and

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Speaker 1: colleagues made an important discovery back in the lab a

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Speaker 1: jumbo phage that can be added to pig feed to

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Speaker 1: selectively weed out salmonella from animals digestive tracks. The hope

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Speaker 1: is that removing salmonella from its source in animals will

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Speaker 1: safeguard food, and doing so will avoid the huge waste

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Speaker 1: associated with dumping food in response to contamination and product recalls,

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Speaker 1: and all of that will reduce the use of antibiotics,

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Speaker 1: both in animals and people, which fosters Drug resistance features

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Speaker 1: are an obvious thing where that you could potentially use

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Speaker 1: to manipulate the microbiome of an animal to remove pathogens

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Speaker 1: or to promote a more health cut microbiome. In a

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Speaker 1: similar way, Professor Clokey is hoping to rid hospital patients

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Speaker 1: of a major bacterial killer. Clostridioidies difficil or seed IF,

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Speaker 1: causes almost half a million diarrheal illnesses and about fifteen

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Speaker 1: thousand deaths annually in the United States alone. Older hospital

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Speaker 1: patients are its prime victims. The miserable life derailing diarrheal

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Speaker 1: disease that seed IF causes usually comes on after friendly

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Speaker 1: intestinal bacteria have been annihilated by a course of antibiotics.

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Speaker 1: Among people over sixty five diagnosed with a healthcare associated

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Speaker 1: sea diff infection, one in eleven is dead within a month.

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Speaker 1: The germ is also really hard to eliminate. Once you've

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Speaker 1: had it, there's a one in five chance of it

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Speaker 1: coming back. It took Professor Cloke in her team three years,

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Speaker 1: tests on hundreds of stool specimens and countless hours of

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Speaker 1: digging our smelly black esterone soils to finally find one.

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Speaker 1: It was a major breakthrough to discover what appear under

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Speaker 1: an electron microscope a little bit like alien creatures. They

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Speaker 1: look a little bit like um somehow, like they come

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Speaker 1: from another world. They have these elegant synurtrical heads and

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Speaker 1: then long, sort of flowing tail fibers. They're just they

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Speaker 1: look a little bit like a a sort of rather

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Speaker 1: unusual insect, but with killer instincts. Those long tail fibers

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Speaker 1: will help the phage find and snare its prey. Once

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Speaker 1: the bacteria is in its grips, the page will inject

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Speaker 1: it's DNA into the cell, and at that point the

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Speaker 1: bacteria is no longer bacteria anymore. It's just a we

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Speaker 1: call a viral factory. It's just making viral particles. After

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Speaker 1: about half an hour will be about maybe fifty for

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Speaker 1: fully formed viral particles in that cell. They then release

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Speaker 1: different enzymes which then breakdown that on the cell or

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Speaker 1: which bust open and the pages will be released. Those

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Speaker 1: new fagures will find new cells on the whole process

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Speaker 1: will repeat itself over again. It's like a biodegradable smart bomb,

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Speaker 1: capable of eliminating a single bacterial target without affecting other

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Speaker 1: beneficial bacteria. So, at least in theory, if you can

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Speaker 1: get a few fags to the site of infection, you

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Speaker 1: then have an institution replication of that medicine to be

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Speaker 1: able to wipe out the infection where it's needed. You

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Speaker 1: can see it's very different to your sort of standard

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Speaker 1: one compound antibiotic lab Experiments with animals that mimic the

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Speaker 1: disease indicate the Professor cloaks phages are adept at killing

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Speaker 1: the main strains of seed if the patients typically contract.

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Speaker 1: They can also inhibit the bacteria when phages are administered

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Speaker 1: days before animals are exposed to see DIF, which suggests

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Speaker 1: they could potentially be given to vulnerable patients to prevent

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Speaker 1: the disease. Professor Cloakey is gathering the basic data needed

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Speaker 1: to demonstrate this safety and efficacy of her pages. She

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Speaker 1: says a prototype product could be ready in about five years. Meantime,

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Speaker 1: researchers and other countries are forging ahead with patient studies

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Speaker 1: aimed at identifying if and how pages could become part

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Speaker 1: of routine medical care. Ironically, in some countries they established

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Speaker 1: that niche early last century. Of US is one of

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Speaker 1: the earliest phage therapy centers is Intability and the former

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Speaker 1: Soviet Republic of Georgia, known as the Eliava Institute, it

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Speaker 1: was the hub for Soviet phage therapy research and production

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Speaker 1: and accumulated the world's largest phage library. It's supplied the

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Speaker 1: Red Army with thousands of treatments to prevent and treat

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Speaker 1: dysentery and wound infections during World War Two, though its

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Speaker 1: products weren't subjected to the kinds of randomized controlled trials

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Speaker 1: usually needed for regulatory approval. Here's Stephanie Stratti again were

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Speaker 1: taken up very vigorously in the former Soviet Union and

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Speaker 1: in parts of Eastern Europe, where they are used to

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Speaker 1: this day. Over the counter even penicillin wasn't so readily

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Speaker 1: available there compared within the West, where antibiotics were considered

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Speaker 1: easier to administer and store. There was also the association

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Speaker 1: with communism during the Cold War that deterred phage research.

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Speaker 1: If you were into phege therapy, were labeled to pinko kami.

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Speaker 1: So this geopolitical bias was a major factor that really

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Speaker 1: delayed the advances in phege therapy that we're starting to

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Speaker 1: recoup now. I was surprised to find out that the

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Speaker 1: US military was working on phage, but it turns out

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Speaker 1: that many different militaries, including the Belgian military, have been

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Speaker 1: working on phige for quite some time. Professor straphanis efforts

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Speaker 1: to save a husband have already drawn attention to a

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Speaker 1: largely neglected and somewhat mistrusted approach to treating infections. In

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Speaker 1: February of two thousand and nineteen, the couple released a

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Speaker 1: about their ordeal. It's called The Perfect Predator, A scientist

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Speaker 1: race to save a husband from a deadly superbug. They

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Speaker 1: recently sold the movie rights to a big Hollywood name.

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Speaker 1: My husband's case was kind of considered to be a

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Speaker 1: watershed moment in the strange history of phage therapy. He

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Speaker 1: certainly wasn't the first person to be treated with phage therapy,

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Speaker 1: but in the United States, he was the first person

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Speaker 1: to receive interveneous phage therapy to treat a systemic superbug

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Speaker 1: infection that was essentially pan resistant. And that knowledge that

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Speaker 1: interveneous phage therapy is safe and those phages, even though

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Speaker 1: we don't really know how they get where they need

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Speaker 1: to go, they know, and so um it's allowing many

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Speaker 1: other cases to be treated. In fact, we estimate forty

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Speaker 1: to fifty people have been treated since Tom's case. For

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Speaker 1: Joe Grimwood, phages arrived just in the nick of time,

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Speaker 1: a year and a half after his phage treatment that

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Speaker 1: preceded his heart transplant. He says he feels like a

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Speaker 1: different man. He has planned is now for things he

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Speaker 1: wouldn't have been able to do two years ago while

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Speaker 1: fighting off infections and waiting for a surgery that never

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Speaker 1: seemed was coming. I'm becoming more active. They told me

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Speaker 1: I can go swimming now, so that'll be fun. I'm

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Speaker 1: not gonna be going bar chestered on the beach. I'll

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Speaker 1: tell you that. How gonna have to episode a T

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Speaker 1: shirt art or something. It's it looks like I got

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Speaker 1: blown up. Ironically, he's probably alive today because of explosions,

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Speaker 1: the microscopic one's going on inside his body thanks to

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Speaker 1: fage therapy. You know I'd saved my life. I guess

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Speaker 1: it is a miracle in a way, and I feel

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Speaker 1: that way. I tell my friends all the time. You know,

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Speaker 1: I'm just watching the miracle unfold well. The cases of

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Speaker 1: Joel Grimwood and Tom Patterson point to the promise of

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Speaker 1: page therapy to find untreatable infections. They don't constitoot scientific

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Speaker 1: evidence that they work. The challenges to apply all the

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Speaker 1: acquired knowledge gathered over the past century to run coordinated,

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Speaker 1: rigorous trials to prove what, if any role phages can

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Speaker 1: play in mitigating the anti microbial resistance crisis. The clock

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Speaker 1: is ticking. It's predicted that unless something drastic happens, one

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Speaker 1: person will die every three seconds from a superbug infection.

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Speaker 1: By the world can't afford to wait more years to

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Speaker 1: find out where the phages can help. And that's it

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Speaker 1: for this week's prognosis. Thanks for listening. Do you have

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Speaker 1: a story about healthcare in the US or around the world.

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Speaker 1: We want to hear from you find me on Twitter

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Speaker 1: at the Cortes or send me an email m Cortes

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Speaker 1: at bloomberg dot net. If you were a fan of

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Speaker 1: this episode, please take a moment to rate and review us.

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Speaker 1: It really helps new listeners find the show and don't

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Speaker 1: forget to subscribe. This episode was produced by Ethan Brooks.

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Speaker 1: Our story editor was Rick Shine. Special thanks to John Lauerman,

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Speaker 1: who helped with the reporting, and Drew Armstrong, our healthcare

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Speaker 1: team leader. Francesco Leavia's head of Bloomberg Podcasts. We'll be

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Speaker 1: back next week with the new episode. See you then,