Speaker 1: As infections become harder to treat because of antibiotic resistance,
Speaker 1: scientists are enlisting help from bacteria's oldest enemy, viruses, so
Speaker 1: called bacteria phases literally, bacteria eaters are viruses that target bacteria.
Speaker 1: While researchers have known about them for a century and
Speaker 1: even use them to treat people, these biological agents have
Speaker 1: been largely ignored in most of the world since penicillin
Speaker 1: became available until recently. That is Welcome to Prognosis, a
Speaker 1: podcast about health and science, medical technology, and the changes
Speaker 1: that are underway across the world. I'm your host, Michelle
Speaker 1: fay Cortes. For our third season, we're delving deeply into
Speaker 1: the human cost of bacterial infections that can't be stopped
Speaker 1: by even our most potent antibiotics. The loss of these
Speaker 1: miracle cures has been described as one of the biggest
Speaker 1: threats to global public health. It spurred a search for
Speaker 1: alternatives to antibiotics. In this episode, Bloomberg's Jason Gale explores
Speaker 1: how that effort is leading scientists back to a Soviet
Speaker 1: era inspired treatment known as phage therapy that's saving the
Speaker 1: lives of patients who couldn't be cured with antibiotics alone.
Speaker 1: He also examines the discoveries being made in some of
Speaker 1: England's smelliest soils that promised to protect us against two
Speaker 1: major sources of deadly disease. Here's Jason. This is Joe Grimwood.
Speaker 1: He's a retired chiropractor who lives at the end of
Speaker 1: a dirt road in the hills outside of Reno, Nevada,
Speaker 1: with Jasmine, his fifty pound bulldog. People terry across and
Speaker 1: more recently an orange second hand track and it's got
Speaker 1: a loader bucket on the front and a scraper on
Speaker 1: the back. It's what they call him midside. So it's
Speaker 1: thirty five horsepower, three cylinder diesel. It's four wheel drive.
Speaker 1: It could lift about eighteen hundred pounds. Joel has big
Speaker 1: plans for it. So we're gonna redo the driveway here
Speaker 1: with it. Well, what I want to do is put
Speaker 1: a garden in over here, and it's you know, at
Speaker 1: least a core acre. Joel is sixty six. He wasn't
Speaker 1: always this active. In fact, a year and a half
Speaker 1: ago he was gravely ill. I practiced chiropractic for over
Speaker 1: twenty years on the north shore Lake Tahoe. In two
Speaker 1: thousand and seven, I had a cardiac arrest and that
Speaker 1: ended that Joel had a diseased hot muscle that put
Speaker 1: him in cardiac failure. Five years ago. He became so
Speaker 1: ill that he needed a hot transplant to buy him
Speaker 1: some time while he waited for a donut. Ogan his
Speaker 1: ductors implying to the mechanical pump known as a left
Speaker 1: ventricular assist device, which is a pump that takes over
Speaker 1: for your left ventricle and pumps blood from your left
Speaker 1: ventricle to your order. The device fitted in Joel's chest
Speaker 1: was powered by an electrical cord that exited his abdomen,
Speaker 1: and this cord it was a direct connection between the
Speaker 1: inside of his heart and the outside world. Despite his
Speaker 1: best efforts to keep it clean, bacteria started growing inside
Speaker 1: the pump. Within a year, Joel was battling a potentially
Speaker 1: deadly infection. I was in all the hospital for three years.
Speaker 1: I was on ivy antibiotics most of that time, and
Speaker 1: they just never could quite knock it out. Surgeons would
Speaker 1: scrape away dead tissue, vacuum up bacteria laden material, and
Speaker 1: sterilize and dress an open wound that gradually grew to
Speaker 1: the size of a key line in Joel's case. Antibiotics
Speaker 1: were subduing the jams in his bloodstream, but we're powerless
Speaker 1: against their mushrooming source, the slime forming bacteria growing on
Speaker 1: his implant. Scientists called the slime bio film. As a
Speaker 1: survival strategy, Bacteria builds structured communities on surfaces, including on
Speaker 1: artificial hips and knees, pacemakers, and catheters, even on airways
Speaker 1: of cystic fibrosis patients. This gunk is a fortress light
Speaker 1: barrier that protects bacteria from antibiotics and the immune system.
Speaker 1: The propensity for bacteria to develop bio films and prosthetic
Speaker 1: implants is a major threat to modern medicine. For instance,
Speaker 1: more than a million knee and hip replacement operations are
Speaker 1: performed annually in the United States alone, and the joint
Speaker 1: infections that result cost more than one billion dollars in
Speaker 1: hospital bills. You know, I was in trouble and I
Speaker 1: is going to die. I was getting out feeling, but
Speaker 1: I never lost the whole, the faith of belief that
Speaker 1: I had survived this. I don't think there was much
Speaker 1: point in thinking any other way. I had to stay positive.
Speaker 1: Joel sent me pictures of what his chest looked like
Speaker 1: without the dressings. His gaping chest wound is about six
Speaker 1: inches long and the color of uncooked steak. I'm not
Speaker 1: especially squeamish, but being able to see directly into his
Speaker 1: body and identify the mushroom shaped base of the pump, well,
Speaker 1: it made me feel nauseous. Joel desperately needed a new heart,
Speaker 1: but the bacterial slime growing on his heart pump made
Speaker 1: a transplant too dangerous. Four hospitals refused to put him
Speaker 1: on the waitlist because of the infection risk. Removing the
Speaker 1: device would dislodge a lethal maelstrom of staff Loococcus aureous bacteria.
Speaker 1: If Joel was going to survive, he needed to get
Speaker 1: rid of the bacteria, and that was impossible with antibiotics alone.
Speaker 1: And the last I'd say six months or so, I
Speaker 1: really got a sense of urgency because it just wasn't
Speaker 1: going away. Hope was dwindling. That is until the fifth
Speaker 1: hospital offered John something Else, a type of experimental treatment
Speaker 1: that had been courageously attempted there a couple of years earlier.
Speaker 1: It was subsequently tried with overall positive results in half
Speaker 1: a dozen patients in much of two thousand and six,
Speaker 1: Californian academic Tom Patterson became the hospital's first recipient. He
Speaker 1: got severely ill with an incurable bacterial infection. He was
Speaker 1: close to dying in the hospital attached to the University
Speaker 1: of California, San Diego, when his wife came up with
Speaker 1: one last option, an approach that flourished in the former
Speaker 1: Soviet Union under Stalinism but hadn't been used in the
Speaker 1: US for generations. And that's page therapy. This is Stephanie Strafty.
Speaker 1: I'm an infectious disease epidemiologist and the Associate Dean of
Speaker 1: Global Health Sciences at UC San Diego, where I also
Speaker 1: co direct a new feage therapy center called iPath. The
Speaker 1: treatment involves using specially selected and prepared viruses to attack
Speaker 1: disease causing bacteria. Professor Strafty took that unconventional approach to
Speaker 1: save her husband Tom, and its success led to Joe
Speaker 1: Grimwood and other patients getting it. In Tom Patterson's case,
Speaker 1: it was a last ditch attempt to keep him alive.
Speaker 1: He had already had seven cases of septic shock, and
Speaker 1: so it was either watch him die or do something
Speaker 1: drastic on my own and I decided to try to
Speaker 1: save his life. Professor Strafty didn't set out to become
Speaker 1: an expert in phage therapy. In fact, she devoted decades
Speaker 1: focusing on the HIV epidemic that got derailed somewhat into
Speaker 1: In sixteen, my husband and I were on vacation in
Speaker 1: Egypt and he acquired what looked like to be a
Speaker 1: stomach bug, but he got violently ill. He was eventually
Speaker 1: met a back to Germany and then back home to
Speaker 1: UC San Diego, where our doctor friends were caring for him,
Speaker 1: and it turned out that he had a gall stone
Speaker 1: that caused a giant abscess in his abdomen, and inside
Speaker 1: that abscess lurked a superbug. The infection was caused by
Speaker 1: a bacterium called a senator. Back to Baumannii, it possessed
Speaker 1: so many drug resistance genes that it was untreatable. Professor
Speaker 1: Stratti says she stopped counting the number of antibodics was given.
Speaker 1: His infection was resistant to fifteen antibiotics right off the bat,
Speaker 1: and it was only partially sensitive to three, and in
Speaker 1: the few weeks that it took to um get him
Speaker 1: back home to San Diego, it acquired resistance to those
Speaker 1: last three antibiotics, including Calliston and mirror pennum, and those
Speaker 1: are considered last resort antibiotics. The bacteria is nicknamed Araqua
Speaker 1: BacT because of the veterans you have returned from the
Speaker 1: Middle East with the infection. This is an organism I
Speaker 1: used to play on my petri dishes back in the
Speaker 1: nineteen eighties at the University of Toronto, and it was
Speaker 1: considered a pretty wimpy organism back then. But it's acquired
Speaker 1: superpowers at the bacterial level because it's almost like a kleptomaniac.
Speaker 1: It steals antibiotic resistance genes from other bacteria, and when
Speaker 1: we're throwing antibiotics at an infection, this one is resistant
Speaker 1: and it's just rubbing its hands together saying, okay, you
Speaker 1: got rid of my competition. Now I can move in
Speaker 1: for the kill and a head Professors straths husband Tom
Speaker 1: firmly in its clutches. He was possibly ours away from death.
Speaker 1: His doctors had given us the talk. They said, basically,
Speaker 1: there's nothing else that we can do. This organism is
Speaker 1: resistant to all antibiotics. Desperate, Professor Strathty clung to something
Speaker 1: she recalled from her undergrad days back in Canada. Well,
Speaker 1: I have a very old degree in microbiology from the
Speaker 1: nineteen eighties, and I had learned in my classes that
Speaker 1: pages are viruses that have naturally evolved to attack bacteria,
Speaker 1: and you can see how they work in a petri dish,
Speaker 1: even though you can't visualize them with your naked eye
Speaker 1: or even with a light microscope. But what I didn't
Speaker 1: know is that pages had been used over a hundred
Speaker 1: years ago to treat people with bacterial infections quite successfully.
Speaker 1: For a time, Professor Strathty worked with scientists in Texas
Speaker 1: and the US military to acquire cocktails of pages that
Speaker 1: matched the bacteria poisoning her husband. Meantime, she worked with
Speaker 1: his doctors and the Food and Drug Administration to gain
Speaker 1: approval to use them on compassionate grounds. The first batch
Speaker 1: arrived from Texas A and M University, and we inserted
Speaker 1: those into the tubes or catheters in his abdomen because
Speaker 1: that was closest to his infection, and we just hoped
Speaker 1: that nothing would happen, because you know, we were worried
Speaker 1: that he could die of septic shock because essentially we
Speaker 1: were injecting a billion viruses into his body and he
Speaker 1: remained stable. So two days later we had phages arrived
Speaker 1: from the Navy, and those pages were considered to be
Speaker 1: more virulent. We injected those pages into his body, a
Speaker 1: billion pages per dose, and that was when he really
Speaker 1: started turning around. While it's impossible to prove that it
Speaker 1: was phage therapy that saved Tom's life, what happened next
Speaker 1: was dramatic. A couple of days after we began intervene
Speaker 1: his phage therapy, he lifted his head off the pillow
Speaker 1: and kissed his daughter's hand, and everybody in the icy
Speaker 1: freaked out, including myself. Doctors observed something very cool in
Speaker 1: Tom's case. The bacteria had to make a genetic decision.
Speaker 1: It could either face the phage or it could face
Speaker 1: anti bio artic and it decided to face the antibiotic,
Speaker 1: so it actually modified itself to become susceptible to antibiotics. Again,
Speaker 1: this synergy between phages and antibiotics has occurred in other patients.
Speaker 1: After phage therapy, their superbug was no longer immune to antibiotics,
Speaker 1: and it's opened up a way of resurrecting failing antibiotic regimens.
Speaker 1: If we can take advantage of the fact that features
Speaker 1: can put selective pressure iron bacteria to make them susceptible
Speaker 1: to some antibiotics. Again, then that would be a really
Speaker 1: important advance. Even if it saves just a couple, that
Speaker 1: could be a very important turning point in this whole
Speaker 1: global crisis that we're facing. In the case of Joel Grimwood,
Speaker 1: whose chest was being slowly consumed by bacterial slime, pages
Speaker 1: are credited with doing something else as equally cool. After
Speaker 1: a four week course of intravenous phage therapy in combination
Speaker 1: with antibiotics, swabs of his open wounds came back negative.
Speaker 1: For staff, it was like it ate the bacteria and
Speaker 1: then when all the bacteria was gone, it just went away.
Speaker 1: It just died. But once I started taking the phage,
Speaker 1: there was a marked improvement in my energy level and
Speaker 1: how I felt. I'd say within a week I started
Speaker 1: to notice differences. Importantly. After four years, some forty surgeries
Speaker 1: and a multitude of medical treatments, he was finally eligible
Speaker 1: for heart transplant surgery. Doctors chalked up his surprising turnaround
Speaker 1: to phage therapy. They qualified me for the transplant, and
Speaker 1: in two weeks I got a heart. Joel Grimwood and
Speaker 1: Tom Patterson epitomized the dramatic results that have revived interest
Speaker 1: in phage therapy to counter untreatable infections. But the basic
Speaker 1: research required to find and developed phage based products that's
Speaker 1: off and frustrating and well sometimes downright gross work. It
Speaker 1: involves getting up close and personal with some large sources
Speaker 1: of bacteria. What we can see here are some really healthy,
Speaker 1: lovely picks. I think they're I think they've lost our
Speaker 1: old spots. This one with the spots. That's Martha Clokey.
Speaker 1: She's a micro biologist who runs a research lab and
Speaker 1: teaches at the University of Leicester, roughly a hundred miles
Speaker 1: north of London. She's responsible for some key phage findings
Speaker 1: that promised to not only improve food safety, but to
Speaker 1: rest a major killer of hospital patients. On an overcast
Speaker 1: summer's day, Professor Clokey is at a farm in East Lake,
Speaker 1: wearing a dark blue cotton dress and looking at a
Speaker 1: pig pen with about a half a dozen animals in it.
Speaker 1: The swine are huge, one bore probably waist close to
Speaker 1: five hundred pounds. But Professor Cloaky isn't here to just
Speaker 1: visit a farm she's hunting pages. It's not what's in
Speaker 1: the pigs that interests her, it's what's beneath them. It's
Speaker 1: a microbial treasure trove comprising soil and pig excrement. We
Speaker 1: get virus like Fluvola eight bacteria of their own viruses
Speaker 1: known as pages. So that's what all our works about,
Speaker 1: is trying to find these very specific bacterial viruses that
Speaker 1: we can then used to treat diseases and animals and humans.
Speaker 1: A quarter of a teaspoon of this smelly stuff will
Speaker 1: harbor tens of billions of bacteria and hundreds of billions
Speaker 1: of pages, which is why farm soils are fertile ground
Speaker 1: for Professor Cloak. So it's a wonderful, natural, lovely microbial
Speaker 1: soupt of bacteria feeding on the on the soil, playing
Speaker 1: all different roles, living off the nutrients, some of which
Speaker 1: are provided by the animals, which is why we often
Speaker 1: findvirus is a target different bacteria the animals carry. So
Speaker 1: it's in order to find good features, we start off
Speaker 1: with a source of healthy animals and we search through
Speaker 1: the soils and feces associated with them, such as this
Speaker 1: sample here. It's immaterial like this that Professor Cloaking and
Speaker 1: colleagues made an important discovery back in the lab a
Speaker 1: jumbo phage that can be added to pig feed to
Speaker 1: selectively weed out salmonella from animals digestive tracks. The hope
Speaker 1: is that removing salmonella from its source in animals will
Speaker 1: safeguard food, and doing so will avoid the huge waste
Speaker 1: associated with dumping food in response to contamination and product recalls,
Speaker 1: and all of that will reduce the use of antibiotics,
Speaker 1: both in animals and people, which fosters Drug resistance features
Speaker 1: are an obvious thing where that you could potentially use
Speaker 1: to manipulate the microbiome of an animal to remove pathogens
Speaker 1: or to promote a more health cut microbiome. In a
Speaker 1: similar way, Professor Clokey is hoping to rid hospital patients
Speaker 1: of a major bacterial killer. Clostridioidies difficil or seed IF,
Speaker 1: causes almost half a million diarrheal illnesses and about fifteen
Speaker 1: thousand deaths annually in the United States alone. Older hospital
Speaker 1: patients are its prime victims. The miserable life derailing diarrheal
Speaker 1: disease that seed IF causes usually comes on after friendly
Speaker 1: intestinal bacteria have been annihilated by a course of antibiotics.
Speaker 1: Among people over sixty five diagnosed with a healthcare associated
Speaker 1: sea diff infection, one in eleven is dead within a month.
Speaker 1: The germ is also really hard to eliminate. Once you've
Speaker 1: had it, there's a one in five chance of it
Speaker 1: coming back. It took Professor Cloke in her team three years,
Speaker 1: tests on hundreds of stool specimens and countless hours of
Speaker 1: digging our smelly black esterone soils to finally find one.
Speaker 1: It was a major breakthrough to discover what appear under
Speaker 1: an electron microscope a little bit like alien creatures. They
Speaker 1: look a little bit like um somehow, like they come
Speaker 1: from another world. They have these elegant synurtrical heads and
Speaker 1: then long, sort of flowing tail fibers. They're just they
Speaker 1: look a little bit like a a sort of rather
Speaker 1: unusual insect, but with killer instincts. Those long tail fibers
Speaker 1: will help the phage find and snare its prey. Once
Speaker 1: the bacteria is in its grips, the page will inject
Speaker 1: it's DNA into the cell, and at that point the
Speaker 1: bacteria is no longer bacteria anymore. It's just a we
Speaker 1: call a viral factory. It's just making viral particles. After
Speaker 1: about half an hour will be about maybe fifty for
Speaker 1: fully formed viral particles in that cell. They then release
Speaker 1: different enzymes which then breakdown that on the cell or
Speaker 1: which bust open and the pages will be released. Those
Speaker 1: new fagures will find new cells on the whole process
Speaker 1: will repeat itself over again. It's like a biodegradable smart bomb,
Speaker 1: capable of eliminating a single bacterial target without affecting other
Speaker 1: beneficial bacteria. So, at least in theory, if you can
Speaker 1: get a few fags to the site of infection, you
Speaker 1: then have an institution replication of that medicine to be
Speaker 1: able to wipe out the infection where it's needed. You
Speaker 1: can see it's very different to your sort of standard
Speaker 1: one compound antibiotic lab Experiments with animals that mimic the
Speaker 1: disease indicate the Professor cloaks phages are adept at killing
Speaker 1: the main strains of seed if the patients typically contract.
Speaker 1: They can also inhibit the bacteria when phages are administered
Speaker 1: days before animals are exposed to see DIF, which suggests
Speaker 1: they could potentially be given to vulnerable patients to prevent
Speaker 1: the disease. Professor Cloakey is gathering the basic data needed
Speaker 1: to demonstrate this safety and efficacy of her pages. She
Speaker 1: says a prototype product could be ready in about five years. Meantime,
Speaker 1: researchers and other countries are forging ahead with patient studies
Speaker 1: aimed at identifying if and how pages could become part
Speaker 1: of routine medical care. Ironically, in some countries they established
Speaker 1: that niche early last century. Of US is one of
Speaker 1: the earliest phage therapy centers is Intability and the former
Speaker 1: Soviet Republic of Georgia, known as the Eliava Institute, it
Speaker 1: was the hub for Soviet phage therapy research and production
Speaker 1: and accumulated the world's largest phage library. It's supplied the
Speaker 1: Red Army with thousands of treatments to prevent and treat
Speaker 1: dysentery and wound infections during World War Two, though its
Speaker 1: products weren't subjected to the kinds of randomized controlled trials
Speaker 1: usually needed for regulatory approval. Here's Stephanie Stratti again were
Speaker 1: taken up very vigorously in the former Soviet Union and
Speaker 1: in parts of Eastern Europe, where they are used to
Speaker 1: this day. Over the counter even penicillin wasn't so readily
Speaker 1: available there compared within the West, where antibiotics were considered
Speaker 1: easier to administer and store. There was also the association
Speaker 1: with communism during the Cold War that deterred phage research.
Speaker 1: If you were into phege therapy, were labeled to pinko kami.
Speaker 1: So this geopolitical bias was a major factor that really
Speaker 1: delayed the advances in phege therapy that we're starting to
Speaker 1: recoup now. I was surprised to find out that the
Speaker 1: US military was working on phage, but it turns out
Speaker 1: that many different militaries, including the Belgian military, have been
Speaker 1: working on phige for quite some time. Professor straphanis efforts
Speaker 1: to save a husband have already drawn attention to a
Speaker 1: largely neglected and somewhat mistrusted approach to treating infections. In
Speaker 1: February of two thousand and nineteen, the couple released a
Speaker 1: about their ordeal. It's called The Perfect Predator, A scientist
Speaker 1: race to save a husband from a deadly superbug. They
Speaker 1: recently sold the movie rights to a big Hollywood name.
Speaker 1: My husband's case was kind of considered to be a
Speaker 1: watershed moment in the strange history of phage therapy. He
Speaker 1: certainly wasn't the first person to be treated with phage therapy,
Speaker 1: but in the United States, he was the first person
Speaker 1: to receive interveneous phage therapy to treat a systemic superbug
Speaker 1: infection that was essentially pan resistant. And that knowledge that
Speaker 1: interveneous phage therapy is safe and those phages, even though
Speaker 1: we don't really know how they get where they need
Speaker 1: to go, they know, and so um it's allowing many
Speaker 1: other cases to be treated. In fact, we estimate forty
Speaker 1: to fifty people have been treated since Tom's case. For
Speaker 1: Joe Grimwood, phages arrived just in the nick of time,
Speaker 1: a year and a half after his phage treatment that
Speaker 1: preceded his heart transplant. He says he feels like a
Speaker 1: different man. He has planned is now for things he
Speaker 1: wouldn't have been able to do two years ago while
Speaker 1: fighting off infections and waiting for a surgery that never
Speaker 1: seemed was coming. I'm becoming more active. They told me
Speaker 1: I can go swimming now, so that'll be fun. I'm
Speaker 1: not gonna be going bar chestered on the beach. I'll
Speaker 1: tell you that. How gonna have to episode a T
Speaker 1: shirt art or something. It's it looks like I got
Speaker 1: blown up. Ironically, he's probably alive today because of explosions,
Speaker 1: the microscopic one's going on inside his body thanks to
Speaker 1: fage therapy. You know I'd saved my life. I guess
Speaker 1: it is a miracle in a way, and I feel
Speaker 1: that way. I tell my friends all the time. You know,
Speaker 1: I'm just watching the miracle unfold well. The cases of
Speaker 1: Joel Grimwood and Tom Patterson point to the promise of
Speaker 1: page therapy to find untreatable infections. They don't constitoot scientific
Speaker 1: evidence that they work. The challenges to apply all the
Speaker 1: acquired knowledge gathered over the past century to run coordinated,
Speaker 1: rigorous trials to prove what, if any role phages can
Speaker 1: play in mitigating the anti microbial resistance crisis. The clock
Speaker 1: is ticking. It's predicted that unless something drastic happens, one
Speaker 1: person will die every three seconds from a superbug infection.
Speaker 1: By the world can't afford to wait more years to
Speaker 1: find out where the phages can help. And that's it
Speaker 1: for this week's prognosis. Thanks for listening. Do you have
Speaker 1: a story about healthcare in the US or around the world.
Speaker 1: We want to hear from you find me on Twitter
Speaker 1: at the Cortes or send me an email m Cortes
Speaker 1: at bloomberg dot net. If you were a fan of
Speaker 1: this episode, please take a moment to rate and review us.
Speaker 1: It really helps new listeners find the show and don't
Speaker 1: forget to subscribe. This episode was produced by Ethan Brooks.
Speaker 1: Our story editor was Rick Shine. Special thanks to John Lauerman,
Speaker 1: who helped with the reporting, and Drew Armstrong, our healthcare
Speaker 1: team leader. Francesco Leavia's head of Bloomberg Podcasts. We'll be
Speaker 1: back next week with the new episode. See you then,