Superbugs' Natural Predator

became available until recently. That is Welcome to Prognosis, a podcast about health and science, medical technology, and the changes that are underway across the world. I'm your host, Michelle fay Cortes. For our third season, we're delving deeply into the human cost of bacterial infections that can't be stopped by even our most potent antibiotics. The loss of these miracle cures has been described as one of the biggest threats to global public health. It spurred a search for

alternatives to antibiotics. In this episode, Bloomberg's Jason Gale explores how that effort is leading scientists back to a Soviet era inspired treatment known as phage therapy that's saving the lives of patients who couldn't be cured with antibiotics alone. He also examines the discoveries being made in some of England's smelliest soils that promised to protect us against two major sources of deadly disease. Here's Jason. This is Joe Grimwood.

He's a retired chiropractor who lives at the end of a dirt road in the hills outside of Reno, Nevada, with Jasmine, his fifty pound bulldog. People terry across and more recently an orange second hand track and it's got a loader bucket on the front and a scraper on the back. It's what they call him midside. So it's thirty five horsepower, three cylinder diesel. It's four wheel drive. It could lift about eighteen hundred pounds. Joel has big plans for it. So we're gonna redo the driveway here

with it. Well, what I want to do is put a garden in over here, and it's you know, at least a core acre. Joel is sixty six. He wasn't always this active. In fact, a year and a half ago he was gravely ill. I practiced chiropractic for over twenty years on the north shore Lake Tahoe. In two thousand and seven, I had a cardiac arrest and that ended that Joel had a diseased hot muscle that put him in cardiac failure. Five years ago. He became so ill that he needed a hot transplant to buy him

some time while he waited for a donut. Ogan his ductors implying to the mechanical pump known as a left ventricular assist device, which is a pump that takes over for your left ventricle and pumps blood from your left ventricle to your order. The device fitted in Joel's chest was powered by an electrical cord that exited his abdomen, and this cord it was a direct connection between the

inside of his heart and the outside world. Despite his best efforts to keep it clean, bacteria started growing inside the pump. Within a year, Joel was battling a potentially deadly infection. I was in all the hospital for three years. I was on ivy antibiotics most of that time, and they just never could quite knock it out. Surgeons would scrape away dead tissue, vacuum up bacteria laden material, and sterilize and dress an open wound that gradually grew to

the size of a key line in Joel's case. Antibiotics were subduing the jams in his bloodstream, but we're powerless against their mushrooming source, the slime forming bacteria growing on his implant. Scientists called the slime bio film. As a survival strategy, Bacteria builds structured communities on surfaces, including on artificial hips and knees, pacemakers, and catheters, even on airways

of cystic fibrosis patients. This gunk is a fortress light barrier that protects bacteria from antibiotics and the immune system. The propensity for bacteria to develop bio films and prosthetic implants is a major threat to modern medicine. For instance, more than a million knee and hip replacement operations are performed annually in the United States alone, and the joint infections that result cost more than one billion dollars in hospital bills. You know, I was in trouble and I

is going to die. I was getting out feeling, but I never lost the whole, the faith of belief that I had survived this. I don't think there was much point in thinking any other way. I had to stay positive. Joel sent me pictures of what his chest looked like without the dressings. His gaping chest wound is about six inches long and the color of uncooked steak. I'm not especially squeamish, but being able to see directly into his body and identify the mushroom shaped base of the pump, well,

it made me feel nauseous. Joel desperately needed a new heart, but the bacterial slime growing on his heart pump made a transplant too dangerous. Four hospitals refused to put him on the waitlist because of the infection risk. Removing the device would dislodge a lethal maelstrom of staff Loococcus aureous bacteria. If Joel was going to survive, he needed to get rid of the bacteria, and that was impossible with antibiotics alone.

And the last I'd say six months or so, I really got a sense of urgency because it just wasn't going away. Hope was dwindling. That is until the fifth hospital offered John something Else, a type of experimental treatment that had been courageously attempted there a couple of years earlier. It was subsequently tried with overall positive results in half a dozen patients in much of two thousand and six, Californian academic Tom Patterson became the hospital's first recipient. He

got severely ill with an incurable bacterial infection. He was close to dying in the hospital attached to the University of California, San Diego, when his wife came up with one last option, an approach that flourished in the former Soviet Union under Stalinism but hadn't been used in the US for generations. And that's page therapy. This is Stephanie Strafty. I'm an infectious disease epidemiologist and the Associate Dean of Global Health Sciences at UC San Diego, where I also

co direct a new feage therapy center called iPath. The treatment involves using specially selected and prepared viruses to attack disease causing bacteria. Professor Strafty took that unconventional approach to save her husband Tom, and its success led to Joe Grimwood and other patients getting it. In Tom Patterson's case, it was a last ditch attempt to keep him alive.

He had already had seven cases of septic shock, and so it was either watch him die or do something drastic on my own and I decided to try to save his life. Professor Strafty didn't set out to become an expert in phage therapy. In fact, she devoted decades focusing on the HIV epidemic that got derailed somewhat into In sixteen, my husband and I were on vacation in Egypt and he acquired what looked like to be a

stomach bug, but he got violently ill. He was eventually met a back to Germany and then back home to UC San Diego, where our doctor friends were caring for him, and it turned out that he had a gall stone that caused a giant abscess in his abdomen, and inside that abscess lurked a superbug. The infection was caused by a bacterium called a senator. Back to Baumannii, it possessed

so many drug resistance genes that it was untreatable. Professor Stratti says she stopped counting the number of antibodics was given. His infection was resistant to fifteen antibiotics right off the bat, and it was only partially sensitive to three, and in the few weeks that it took to um get him back home to San Diego, it acquired resistance to those last three antibiotics, including Calliston and mirror pennum, and those

are considered last resort antibiotics. The bacteria is nicknamed Araqua BacT because of the veterans you have returned from the Middle East with the infection. This is an organism I used to play on my petri dishes back in the nineteen eighties at the University of Toronto, and it was considered a pretty wimpy organism back then. But it's acquired superpowers at the bacterial level because it's almost like a kleptomaniac.

It steals antibiotic resistance genes from other bacteria, and when we're throwing antibiotics at an infection, this one is resistant and it's just rubbing its hands together saying, okay, you got rid of my competition. Now I can move in for the kill and a head Professors straths husband Tom firmly in its clutches. He was possibly ours away from death. His doctors had given us the talk. They said, basically, there's nothing else that we can do. This organism is

resistant to all antibiotics. Desperate, Professor Strathty clung to something she recalled from her undergrad days back in Canada. Well, I have a very old degree in microbiology from the nineteen eighties, and I had learned in my classes that pages are viruses that have naturally evolved to attack bacteria, and you can see how they work in a petri dish, even though you can't visualize them with your naked eye

or even with a light microscope. But what I didn't know is that pages had been used over a hundred years ago to treat people with bacterial infections quite successfully. For a time, Professor Strathty worked with scientists in Texas and the US military to acquire cocktails of pages that matched the bacteria poisoning her husband. Meantime, she worked with his doctors and the Food and Drug Administration to gain

approval to use them on compassionate grounds. The first batch arrived from Texas A and M University, and we inserted those into the tubes or catheters in his abdomen because that was closest to his infection, and we just hoped that nothing would happen, because you know, we were worried that he could die of septic shock because essentially we were injecting a billion viruses into his body and he

remained stable. So two days later we had phages arrived from the Navy, and those pages were considered to be more virulent. We injected those pages into his body, a billion pages per dose, and that was when he really started turning around. While it's impossible to prove that it was phage therapy that saved Tom's life, what happened next

was dramatic. A couple of days after we began intervene his phage therapy, he lifted his head off the pillow and kissed his daughter's hand, and everybody in the icy freaked out, including myself. Doctors observed something very cool in Tom's case. The bacteria had to make a genetic decision. It could either face the phage or it could face anti bio artic and it decided to face the antibiotic,

so it actually modified itself to become susceptible to antibiotics. Again, this synergy between phages and antibiotics has occurred in other patients. After phage therapy, their superbug was no longer immune to antibiotics, and it's opened up a way of resurrecting failing antibiotic regimens. If we can take advantage of the fact that features can put selective pressure iron bacteria to make them susceptible to some antibiotics. Again, then that would be a really

important advance. Even if it saves just a couple, that could be a very important turning point in this whole global crisis that we're facing. In the case of Joel Grimwood, whose chest was being slowly consumed by bacterial slime, pages are credited with doing something else as equally cool. After a four week course of intravenous phage therapy in combination with antibiotics, swabs of his open wounds came back negative.

For staff, it was like it ate the bacteria and then when all the bacteria was gone, it just went away. It just died. But once I started taking the phage, there was a marked improvement in my energy level and how I felt. I'd say within a week I started to notice differences. Importantly. After four years, some forty surgeries and a multitude of medical treatments, he was finally eligible for heart transplant surgery. Doctors chalked up his surprising turnaround

to phage therapy. They qualified me for the transplant, and in two weeks I got a heart. Joel Grimwood and Tom Patterson epitomized the dramatic results that have revived interest in phage therapy to counter untreatable infections. But the basic research required to find and developed phage based products that's off and frustrating and well sometimes downright gross work. It involves getting up close and personal with some large sources of bacteria. What we can see here are some really healthy,

lovely picks. I think they're I think they've lost our old spots. This one with the spots. That's Martha Clokey. She's a micro biologist who runs a research lab and teaches at the University of Leicester, roughly a hundred miles north of London. She's responsible for some key phage findings that promised to not only improve food safety, but to

rest a major killer of hospital patients. On an overcast summer's day, Professor Clokey is at a farm in East Lake, wearing a dark blue cotton dress and looking at a pig pen with about a half a dozen animals in it. The swine are huge, one bore probably waist close to five hundred pounds. But Professor Cloaky isn't here to just visit a farm she's hunting pages. It's not what's in the pigs that interests her, it's what's beneath them. It's

a microbial treasure trove comprising soil and pig excrement. We get virus like Fluvola eight bacteria of their own viruses known as pages. So that's what all our works about, is trying to find these very specific bacterial viruses that we can then used to treat diseases and animals and humans. A quarter of a teaspoon of this smelly stuff will harbor tens of billions of bacteria and hundreds of billions of pages, which is why farm soils are fertile ground

for Professor Cloak. So it's a wonderful, natural, lovely microbial soupt of bacteria feeding on the on the soil, playing all different roles, living off the nutrients, some of which are provided by the animals, which is why we often findvirus is a target different bacteria the animals carry. So it's in order to find good features, we start off with a source of healthy animals and we search through the soils and feces associated with them, such as this

sample here. It's immaterial like this that Professor Cloaking and colleagues made an important discovery back in the lab a jumbo phage that can be added to pig feed to

selectively weed out salmonella from animals digestive tracks. The hope is that removing salmonella from its source in animals will safeguard food, and doing so will avoid the huge waste associated with dumping food in response to contamination and product recalls, and all of that will reduce the use of antibiotics, both in animals and people, which fosters Drug resistance features are an obvious thing where that you could potentially use

to manipulate the microbiome of an animal to remove pathogens or to promote a more health cut microbiome. In a similar way, Professor Clokey is hoping to rid hospital patients of a major bacterial killer. Clostridioidies difficil or seed IF, causes almost half a million diarrheal illnesses and about fifteen thousand deaths annually in the United States alone. Older hospital

patients are its prime victims. The miserable life derailing diarrheal disease that seed IF causes usually comes on after friendly intestinal bacteria have been annihilated by a course of antibiotics. Among people over sixty five diagnosed with a healthcare associated sea diff infection, one in eleven is dead within a month. The germ is also really hard to eliminate. Once you've had it, there's a one in five chance of it

coming back. It took Professor Cloke in her team three years, tests on hundreds of stool specimens and countless hours of digging our smelly black esterone soils to finally find one. It was a major breakthrough to discover what appear under an electron microscope a little bit like alien creatures. They look a little bit like um somehow, like they come from another world. They have these elegant synurtrical heads and

then long, sort of flowing tail fibers. They're just they look a little bit like a a sort of rather unusual insect, but with killer instincts. Those long tail fibers will help the phage find and snare its prey. Once the bacteria is in its grips, the page will inject it's DNA into the cell, and at that point the bacteria is no longer bacteria anymore. It's just a we call a viral factory. It's just making viral particles. After about half an hour will be about maybe fifty for

fully formed viral particles in that cell. They then release different enzymes which then breakdown that on the cell or which bust open and the pages will be released. Those new fagures will find new cells on the whole process will repeat itself over again. It's like a biodegradable smart bomb, capable of eliminating a single bacterial target without affecting other

beneficial bacteria. So, at least in theory, if you can get a few fags to the site of infection, you then have an institution replication of that medicine to be able to wipe out the infection where it's needed. You can see it's very different to your sort of standard one compound antibiotic lab Experiments with animals that mimic the disease indicate the Professor cloaks phages are adept at killing the main strains of seed if the patients typically contract.

They can also inhibit the bacteria when phages are administered days before animals are exposed to see DIF, which suggests they could potentially be given to vulnerable patients to prevent the disease. Professor Cloakey is gathering the basic data needed to demonstrate this safety and efficacy of her pages. She

says a prototype product could be ready in about five years. Meantime, researchers and other countries are forging ahead with patient studies aimed at identifying if and how pages could become part of routine medical care. Ironically, in some countries they established

that niche early last century. Of US is one of the earliest phage therapy centers is Intability and the former Soviet Republic of Georgia, known as the Eliava Institute, it was the hub for Soviet phage therapy research and production and accumulated the world's largest phage library. It's supplied the Red Army with thousands of treatments to prevent and treat dysentery and wound infections during World War Two, though its products weren't subjected to the kinds of randomized controlled trials

usually needed for regulatory approval. Here's Stephanie Stratti again were taken up very vigorously in the former Soviet Union and in parts of Eastern Europe, where they are used to this day. Over the counter even penicillin wasn't so readily available there compared within the West, where antibiotics were considered easier to administer and store. There was also the association with communism during the Cold War that deterred phage research.

If you were into phege therapy, were labeled to pinko kami. So this geopolitical bias was a major factor that really delayed the advances in phege therapy that we're starting to recoup now. I was surprised to find out that the US military was working on phage, but it turns out that many different militaries, including the Belgian military, have been working on phige for quite some time. Professor straphanis efforts to save a husband have already drawn attention to a

largely neglected and somewhat mistrusted approach to treating infections. In February of two thousand and nineteen, the couple released a about their ordeal. It's called The Perfect Predator, A scientist race to save a husband from a deadly superbug. They recently sold the movie rights to a big Hollywood name. My husband's case was kind of considered to be a

watershed moment in the strange history of phage therapy. He certainly wasn't the first person to be treated with phage therapy, but in the United States, he was the first person to receive interveneous phage therapy to treat a systemic superbug infection that was essentially pan resistant. And that knowledge that interveneous phage therapy is safe and those phages, even though we don't really know how they get where they need to go, they know, and so um it's allowing many

other cases to be treated. In fact, we estimate forty to fifty people have been treated since Tom's case. For Joe Grimwood, phages arrived just in the nick of time, a year and a half after his phage treatment that preceded his heart transplant. He says he feels like a different man. He has planned is now for things he wouldn't have been able to do two years ago while fighting off infections and waiting for a surgery that never seemed was coming. I'm becoming more active. They told me

I can go swimming now, so that'll be fun. I'm not gonna be going bar chestered on the beach. I'll tell you that. How gonna have to episode a T shirt art or something. It's it looks like I got blown up. Ironically, he's probably alive today because of explosions, the microscopic one's going on inside his body thanks to fage therapy. You know I'd saved my life. I guess it is a miracle in a way, and I feel that way. I tell my friends all the time. You know,

I'm just watching the miracle unfold well. The cases of Joel Grimwood and Tom Patterson point to the promise of page therapy to find untreatable infections. They don't constitoot scientific evidence that they work. The challenges to apply all the acquired knowledge gathered over the past century to run coordinated, rigorous trials to prove what, if any role phages can play in mitigating the anti microbial resistance crisis. The clock

is ticking. It's predicted that unless something drastic happens, one person will die every three seconds from a superbug infection. By the world can't afford to wait more years to find out where the phages can help. And that's it for this week's prognosis. Thanks for listening. Do you have a story about healthcare in the US or around the world. We want to hear from you find me on Twitter at the Cortes or send me an email m Cortes

at bloomberg dot net. If you were a fan of this episode, please take a moment to rate and review us. It really helps new listeners find the show and don't forget to subscribe. This episode was produced by Ethan Brooks. Our story editor was Rick Shine. Special thanks to John Lauerman, who helped with the reporting, and Drew Armstrong, our healthcare team leader. Francesco Leavia's head of Bloomberg Podcasts. We'll be back next week with the new episode. See you then,