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Speaker 1: Hi, Prognosis listeners, this is your host, Michelle fay Cortes.

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Speaker 1: We've spent this month looking back at some of our

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Speaker 1: favorite stories from the podcast. For our last rebroadcast, we

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Speaker 1: hear how scientists are trying to revive a long forgotten

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Speaker 1: technology once popular in the former Soviet Union in a

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Speaker 1: desperate effort to combat superbugs, thanks and enjoy. As infections

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Speaker 1: become harder to treat because of antibiotic resistance, scientists are

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

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

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

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

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

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

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

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

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Speaker 1: For our third season, we're delving deeply into the human

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Speaker 1: cost of bacterial infections that can't be stopped by even

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Speaker 1: our most potent antibiotics. The loss of these miracle cures

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Speaker 1: has been described as one of the biggest threats to

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

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Speaker 1: In this episode, Bloomberg's Jason Gale explores how that effort

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Speaker 1: is leading scientists back to a Soviet era inspired treatment

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Speaker 1: known as phage therapy, that saving the lives of patients

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Speaker 1: who couldn't be cured with antibiotics alone. He also examines

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Speaker 1: the discoveries being made in some of England's smelliest soils

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Speaker 1: that promised to protect us against two made your sources

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

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

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Speaker 1: debt road in the hills outside of Reno, Nevada, with Jasmine,

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Speaker 1: his fifty pound bulldog pit bull Terry Across and more

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Speaker 1: recently an orange second hand tractor. And it's got a

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

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Speaker 1: It's what they call a midside so it's thirty five horsepower,

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Speaker 1: three cylinder diesel. It's four wheel drive. It can lift

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Speaker 1: about eighteen hundred pounds. Joel has big plans for it.

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Speaker 1: What I want to do is put a garden in

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Speaker 1: over here, and it's you know, at least a core

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Speaker 1: or acre. Joel is sixty six. He wasn't always this active.

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Speaker 1: In fact, a year and a half ago he was

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Speaker 1: gravely ill. I practice chiropractic for over twenty years on

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Speaker 1: the north Shore like Tahoe. In two thousand and seven,

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Speaker 1: I had a cardiac arrest and that ended that. Joel

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Speaker 1: had a diseased heart muscle that put him in cardiac failure.

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Speaker 1: Five years ago, he became so ill that he needed

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Speaker 1: a heart transplant to buy him some time. While he

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Speaker 1: waited for a donut organ, his doctors implanted a mechanical

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Speaker 1: pump known as a left ventricular assist device, which is

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Speaker 1: a pump that takes over for your left ventricle and

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Speaker 1: pumps blood from your left ventricle to your order. The

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Speaker 1: device fitted in Joel's chest was powered by an electrical

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Speaker 1: cord that exited his abdomen, and this cord it was

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Speaker 1: a direct connection between the inside of his heart and

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Speaker 1: the outside world. Despite his best efforts to keep it clean,

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Speaker 1: bacteria started growing inside the pump. Within a year, Joel

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Speaker 1: was battling a potentially deadly infection was in all the

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Speaker 1: hospital for three years. I was on ivy antibiotics most

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Speaker 1: of that time, and they just never could quite knock

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Speaker 1: it out. Surgeons would scrape away dead tissue, vacuum up

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Speaker 1: bacteria laid in material, and sterilize and dress an open

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Speaker 1: wound that gradually grew to the size of a key line.

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Speaker 1: In Joel's case, antibiotics were subduing the gems in his bloodstream,

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Speaker 1: but we're powerless against their mushrooming source, the slime forming

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Speaker 1: bacteria growing on his implant. Scientists called the slime bio film.

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Speaker 1: As a survival strategy, bacteria builds structured communities on surfaces,

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

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Speaker 1: on airways of cystic fibrosis patients. This gunk is a

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Speaker 1: fortress light barrier that protects bacteria from antibiotics and the

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Speaker 1: immune system. The propensity for bacteria to develop bio films

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Speaker 1: and prosthetic implants is a major threat to modern medicine.

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Speaker 1: For instance, more than a million knee and hip replacement

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

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

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

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Speaker 1: I was going to die. I was getting that feeling,

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Speaker 1: but I never lost the whope, the faith of belief

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

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

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Speaker 1: stay positive. Joel sent me pictures of what his chest

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Speaker 1: looked like without the dressings. His gaping chest wound is

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Speaker 1: about six inches long and the color of uncooked steak.

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Speaker 1: I'm not especially squeamish, but being able to see directly

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Speaker 1: into his body and identify the mushroom shaped base of

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Speaker 1: the pump, well, it made me feel nauseous. Joel desperately

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Speaker 1: needed a new heart, but the bacterial slide growing on

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Speaker 1: his heart pump made a transplant too dangerous. Four hospitals

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Speaker 1: refused to put him on the waitlist because of the

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Speaker 1: infection risk. Removing the device would dislodge a lethal maelstrom

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Speaker 1: of staff Loococcus aureus bacteria. If Joel was going to survive,

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Speaker 1: he needed to get rid of the bacteria, and that

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Speaker 1: was impossible with antibiotics alone. And the last I'd say

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Speaker 1: six months or so, I really got a sense of

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Speaker 1: urgency because it just wasn't going away. Hope was dwindling,

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Speaker 1: that is until the fifth hospital offered John something Else,

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Speaker 1: a type of experimental treatment that had been courageously attempted

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Speaker 1: there a couple of years earlier. It was subsequently tried

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Speaker 1: with overall positive results in half a dozen patients in

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Speaker 1: much of two thousand and six, California academic Tom Patterson

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Speaker 1: became the hospital's first recipient. He got severely ill with

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Speaker 1: an incurable bacterial infection. He was close to dying in

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Speaker 1: the hospital attached to the University of California, San Diego

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Speaker 1: when his wife came up with one last option, an

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Speaker 1: approach that flourished in the former Soviet Union under stalinism

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Speaker 1: but hadn't been used in the US for generations, and

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Speaker 1: that speech therapy. This is Stephanie Strafty, an infectious disease

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Speaker 1: epidemiologist and the Associate Dean of Global Health Sciences at

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Speaker 1: UC San Diego, where I also co direct a new

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Speaker 1: feage therapy center called iPath. The treatment involves using specially

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Speaker 1: selected and prepared viruses to attack disease causing bacteria. Professor

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Speaker 1: Stratti took that unconventional approach to save her husband Tom

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Speaker 1: and its success led to Joe Grimwood and other patients

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Speaker 1: getting it. In Tom Patterson's case, it was a last

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Speaker 1: ditch attempt to keep him alive. He had already had

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Speaker 1: in seven cases of septic shark and so it was

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Speaker 1: either watch him die or do something drastic on my own,

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Speaker 1: and I decided to try to save his life. Professor

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Speaker 1: Strafti didn't send out to become an expert in phage therapy.

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Speaker 1: In fact, she devoted decades focusing on the HIV epidemic

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Speaker 1: that got derailed somewhat. In two thousand and sixteen, my

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Speaker 1: husband and I were on vacation in Egypt and he

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Speaker 1: acquired what looked like to be a stomach bug, but

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Speaker 1: he got violently ill. He was eventually met a back

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Speaker 1: to Germany and then back home to u C. San Diego,

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Speaker 1: where our doctor friends were caring for him, and it

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Speaker 1: turned out that he had a gallstone that caused a

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Speaker 1: giant absence in his abdomen, and inside that abscess lurked

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Speaker 1: a superbug. The infection was caused by a bacterium called

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Speaker 1: a senator. Back to beaumani I, it possessed so many

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Speaker 1: drug resistance genes that it was untreatable. Professor Strati says

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Speaker 1: she stopped counting the number of antibodics husband 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 bacterium is nicknamed Roqua

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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 it on my petri dishes back in

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

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

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Speaker 1: acquired superpowers at the bacterial level because it's almost like

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Speaker 1: a kleptomaniac. It steals antibiotic resistance genes from other bacteria,

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Speaker 1: and when we're throwing antibiotics at an infection, this one

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

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

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Speaker 1: in for the kill and a head Professor Strattis husband

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Speaker 1: Tom firmal in its clutches. He was possibly hours away

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Speaker 1: from death. 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, Professors Strafe 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 Strafti 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 aked 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: the antibiotic, and it decided to face the antibiotics, so

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Speaker 1: 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 pages

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Speaker 1: can put selective pressure on 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 a eight 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. It's a counter untreatable infections, but the

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Speaker 1: basic research required to find and developed phage based products

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Speaker 1: that's often 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 there. I think they've lost our

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Speaker 1: old spots. This one's on there with the spots pot.

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Speaker 1: That's Martha Clerky. She's a micro biologist who runs a

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Speaker 1: key phage findings that promised to not only improve food

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Speaker 1: an overcast summer's day, Professor Cloakey is at a farm

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Speaker 1: in East Lake, wearing a dark blue cotton dress and

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Speaker 1: looking at a pig pen with about a half a

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Speaker 1: probably weighs close to five hundred pounds. But Professor Cloakey

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Speaker 1: isn't here to just visit a farm. She's hunting pages.

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Speaker 1: It's not what's in the pigs that interests her, it's

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Speaker 1: what's beneath them. It's a microbial treasure trove comprising soil

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Speaker 1: and pig excrement. We get virus like fluo eight bacteria

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Speaker 1: of their own viruses known as pages. So that's what

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Speaker 1: specific bacterial viruses that we can then used to treat

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Speaker 1: diseases and animals and humans. A quarter of a teaspoon

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Speaker 1: of this smelly stuff will harbor tens of billions of

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Speaker 1: bacteria and hundreds of billions of pages, which is why

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Speaker 1: farm soils are fertile ground for Professor cloak So it's

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Speaker 1: a wonderful, natural, lovely microbial soup, all bacteria feeding on

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Speaker 1: the on the soil, playing all different roles, living off

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Speaker 1: the nutrients, some of which are provided by the animals,

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Speaker 1: which is why we often find viruses at target different

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Speaker 1: bacteria the animals curry. So in order to find good pages,

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Speaker 1: we start off with a source of healthy animals and

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Speaker 1: we search through the soils and feces associated with them,

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Speaker 1: such as this sample here. It's immaterial like this that

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Speaker 1: Professor Cloak and colleagues made an important discovery back in

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Speaker 1: the lab, a jumbo phage that can be added to

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Speaker 1: pig feed to selectively weed out salmonilla from animals digestive tracks.

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Speaker 1: The hope is that removing salmonella from its source in

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

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Speaker 1: huge waste associated with dumping food in response to contamination

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Speaker 1: and product recalls, and all of that will reduce the

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Speaker 1: use of antibiotics, both in animals and people, which fosters

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Speaker 1: Drug resistance features are an obvious thing where that you

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Speaker 1: could potentially use to manipulate the microbiome of an animal

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Speaker 1: In a similar way, Professor Clokey is hoping to read

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Speaker 1: hospital patients of a major bacterial killer Clostridioides difficil, or

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Speaker 1: seed IF, causes almost half a million diarrheal illnesses and

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Speaker 1: about fifteen thousand deaths annually in the United States alone.

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Speaker 1: Older hospital patients are its prime victims. The miserable life

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Speaker 1: derailing diarrheal disease that seed IF causes usually comes on

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Speaker 1: after a friendly intestinal bacteria have been annihilated by a

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Speaker 1: course of antibiotics. Among people over sixty five diagnosed with

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Speaker 1: a healthcare associated see differ infection, one in eleven is

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Speaker 1: dead within a month. The germ is also really hard

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Speaker 1: to eliminate. Once you've had it, there's a one in

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Speaker 1: five chance of it coming back. It took Professor Cloaky

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Speaker 1: in her team three years, tests on hundreds of stool

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Speaker 1: specimens and countless hours of digging up smelly black esterone

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Speaker 1: soils to finally find one. It was a major breakthrough

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Speaker 1: to discover what appear under an electron microscope a little

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Speaker 1: bit like alien creatures. They look a little bit like

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Speaker 1: um somehow, like they come from another world. They have

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Speaker 1: these elegant snurgrical heads and them long sort of flowing

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Speaker 1: tail fibers. They're just they look a little bit like

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Speaker 1: a a sort of rather unusual insect, but with killer instincts.

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Speaker 1: Those long tail fibers will help the phage find and

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Speaker 1: snare its prey. Once the bacteria is in its grips,

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Speaker 1: the page will inject it's DNA into the cell, and

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Speaker 1: at that point the bacteria is no longer bacteria anymore.

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Speaker 1: It's just a we call a viral factory. It's just

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Speaker 1: making viral particles. After about half an hour will be

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Speaker 1: about maybe fifty full fully formed viral particles in that cell.

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Speaker 1: They then release different enzymes which then break down that

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Speaker 1: cell in the cell, or which bust open, and the

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Speaker 1: phages will be released. Those new pages will find new

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Speaker 1: cells on the whole process will repeat itself over again.

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Speaker 1: It's like a biodegradable smart bomb, capable of eliminating a

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Speaker 1: single bacterial target without affecting other beneficial bacteria. So, at

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Speaker 1: least in theory, if you can get a few pages

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Speaker 1: to the site of infection, you then have an institution

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Speaker 1: replication of that medicine to be able to wipe out

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Speaker 1: the infection where it's needed. You can see it's very

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Speaker 1: different to your sort of standard one compound antibiotic lab

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Speaker 1: experiments with animals that mimic the disease, indicate the Professor cloaks,

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Speaker 1: phages are adept at killing the mains rains of seed

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Speaker 1: if the patients typically contract. They can also inhibit the

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Speaker 1: bacteria when pages are administered days before animals are exposed

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Speaker 1: to see diff which suggests they could potentially be given

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Speaker 1: to vulnerable patients to prevent the disease. Professor Clerk is

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Speaker 1: gathering the basic data needed to demonstrate the safety and

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Speaker 1: efficacy of her pages. She says a prototype product could

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Speaker 1: be ready in about five years. Meantime, researchers in other

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Speaker 1: countries are forging ahead with patient studies aimed at identifying

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Speaker 1: if and how phages could become part of routine medical care. Ironically,

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Speaker 1: in some countries they established that niche early last century

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Speaker 1: of us is did look up. One of the earliest

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Speaker 1: phage therapy centers is Intability and the former Soviet Republic

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Speaker 1: of Georgia, known as the Eliava Institute. It was the

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Speaker 1: hub for Soviet phage therapy research and production and accumulate

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Speaker 1: did the world's largest phage library. It's supplied the Red

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

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

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Speaker 1: weren't subjected to the klins of randomized controlled trials usually

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Speaker 1: needed for regulatory approval. He's definitely stratti Again. They 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 pege therapy, were lable to pink

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Speaker 1: o kami. So this geopolitical bias was a major factor

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Speaker 1: that really delayed the advances in pege therapy that we're

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

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Speaker 1: that the US military was working on fair age, but

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Speaker 1: it turns out that many different militaries, including the Belgian military,

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Speaker 1: have been working on phage for quite some time. Professor

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

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

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

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Speaker 1: a book about their ordeal. It's called The Perfect Predator,

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

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Speaker 1: They 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 intravenous 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: intravenous 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 for

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Speaker 1: fifty people have been treated since Tom's case. For Joel Grimwood,

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Speaker 1: Pages arrived just in the nick of time, a year

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Speaker 1: and a half after his Page treatment that preceded his

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Speaker 1: heart transplant. He says he feels like a different man.

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Speaker 1: He has plans now for things he wouldn't have been

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Speaker 1: able to do two years ago, while fighting off infections

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Speaker 1: and waiting for a surgery that never seemed was coming.

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Speaker 1: I'm becoming more active. They told me I can go

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Speaker 1: swimming now, so that'll be fun. I'm not going to

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Speaker 1: be uh going bar chested on the beach. I'll tell

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Speaker 1: you that. How gonna have to have so 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. You away, and I feel that way.

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Speaker 1: I tell my friends all the time. You know, I'm

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Speaker 1: just watching the miracle unfold. All the cases of Joel

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

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Speaker 1: therapy to find untreatable infections. They don't constitute scientific evidence

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

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

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

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

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Speaker 1: It's predicted that unless something drastic happens, one person will

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Speaker 1: die every three seconds from a superbug infection. By the

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Speaker 1: world can't afford to wait more years to find out

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Speaker 1: where the phages can help. And that's it for this

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

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Speaker 1: about healthcare in the US or around the world we

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Speaker 1: want to hear from you. Find me on Twitter at

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

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Speaker 1: Bloomberg dot net. If you were a fan of this episode,

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Speaker 1: please take a moment to rate and review us. It

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

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

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

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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,