'Hey there. It's Sanjay. I wanted to share an important story that I reported on recently for CNN. As you probably know, antibiotic resistance is a growing problem around the world. It's been that way for decades. While drug developers scramble to find the next new antibiotics to fight these so-called superbugs, there is a loose coalition of scientists who are now taking a different approach. In a sense, what they're doing is pitting two of humankind's microscopic enemies against each other. Viruses versus bacteria. And they're not just any viruses. The researchers are talking about phages. These are viruses that attack and eat dangerous bacteria. There are trillions of these phages out there just waiting to be discovered and deployed. Now, the story starts with one woman's desperate attempt to save her husband's life. Antibiotics had failed to clear up a resistant infection that was now killing him. It was a scientific breakthrough that changed the trajectory of medicine. 1928 Alexander Fleming discovered penicillin in a London lab. It was quickly hailed as a miracle drug. Since then, antibiotics have no question been widely used to save countless lives.
They're very effective and simple to use in general for treating bacterial infections.
But not even 100 years later, the bugs have fought back. They have become superbugs.
The pipeline for new antibiotics is drying up.
We're really behind the eight ball because one person every three seconds is going to be dying of a superbug by 2050.
Researchers have shown me how they are scouring the world trying to find alternate solutions.
We need alternatives and we need adjuncts to antibiotics.
Could the answer have been under our noses all along?
I'm never going to look at nature quite the same way. So this is a nice spot.
It's a great place where there's a lot of water running off. And it's accessible.
Today, Epidemiologist Steffanie Strathdee is taking me on a hunt for what are known as phages. They are naturally occurring viruses that have a special quality. They eat bacteria. And in many ways, Stephanie says they are perfect predators. And although phages can be found almost anywhere, the dirtier the location, the better.
Steffanie Strathdee
00:02:35
If I see any poop, I go close to that.
Any idea of how many phages would potentially be in there?
Steffanie Strathdee
00:02:42
Well, one drop of water can have up to a trillion phages in it.
Which means a trillion possibilities that this dirty water could be used to treat an infection for which we currently have no therapy. Superbugs. Think of them as strains of bacteria, viruses, parasites, even fungi that have developed resistance to medications. Even the medications going all the way back to Fleming's penicillin, making these superbugs at times impossible to treat at all. You see, the very enthusiasm for these drugs is also what led to their downfall. Because the more we use them, the more chances these pathogens have to learn, adapt, mutate to create their own defense systems. It only took a few years after penicillin was first used to see penicillin resistant bacteria first start popping up. And now, in the United States alone, the U.S. Centers for Disease Control and Prevention estimate there are more than 2.8 million of these antimicrobial resistant infections each year. It's why these ships scour the Arctic waters looking to the depths of the ocean for naturally occurring new antibiotics. It is why billions of dollars are spent in labs to try and create new drugs, in why hospitals are trying to use antibiotics with more restraint. And yet, despite all that, we are losing the race. It's something that drives Stephanie Strathy to try more, let's say, unconventional approaches.
Steffanie Strathdee
00:04:19
If we got 4 or 5 vaccines for Covid in a year, surely we can come together as humans and help each other solve the superbug crisis. All right. Well, that ought to do it.
I think anybody who's watching this is going to have a different perspective on on looking at what they would typically ignore, waste that they think has no value. Yeah. And instead, you know, the idea that it, again, could be medicine.
Steffanie Strathdee
00:04:45
Just think of all the people that could be saved from the pages in here.
Now, you may be wondering why you've never heard of phages before. After all, the bacteria killing virus was discovered more than a century ago. It's been used throughout Eastern Europe and Russia for decades now.
Steffanie Strathdee
00:05:03
Phage were discovered before penicillin was discovered.
But despite these discoveries, phage therapy has never been widely adopted in the West.
Steffanie Strathdee
00:05:12
Phage were being used at around the time that the Second World War was starting, and when they were really embraced by the former Soviet Union, that was seen as something that was Soviet science, Soviet medicine.
It was geopolitics exerting its influence over science and medicine. But Stephanie, she didn't care about any of that. Almost ten years ago, she found herself with nowhere else to turn. And how did you ignite your interest in this?
Steffanie Strathdee
00:05:42
Well, it certainly is something that I kind of fell into.
It's quite a story. And like so many amazing stories, it starts with love. Married in 2004, Tom, the professor and Stephanie, the epidemiologist, shared a passion for travel and adventure around the world to more than 50 countries together. And it was on one of these trips in Egypt that the story of Stephanie, Tom and phages all came colliding together.
Steffanie Strathdee
00:06:16
He had what I thought was food poisoning and was feeling absolutely terrible and really just, you know, vomiting and, you know, just feeling awful. And it wasn't getting any better.
Steffanie Strathdee
00:06:28
The clinic diagnosed pancreatitis. It was caused by a gallstone that blocked his bile duct and caused a giant abscess to form. But that wasn't the worst of it because that abscess made a nice little apartment for this superbug to move into.
Tom had contracted Acinetobacter. Baumannii. Now, you don't need to remember the name. All you need to know is that it was one of those superbugs almost impossible to treat, and it quickly wreaked havoc on his body. You thought he wasn't going to make it?
Steffanie Strathdee
00:06:58
I was told by the doctor. That he wasn't going to make it. He was on a ventilator because his lungs were failing. He was on three different medications to keep his heart pumping and his kidneys were hanging on by a thread.
Were you able to communicate with Tom at this point?
Steffanie Strathdee
00:07:11
'I asked him if he wanted to live and to squeeze my hand if he did. They squeezed it really hard, and so I was excited and I ran home and I started doing research on my own to figure out what we could do. I put the keywords like the name of his superbug and alternative treatments and multi-drug resistance as keywords. And up popped a paper that had buried in it phage therapy.
It was a start. But remember, with trillions upon trillions of phages in the world, finding the right phage for a specific infection, that's the real challenge. Think of it as an endless number of keys for just one lock. Stephanie was essentially searching for a needle in a haystack. So she enlisted scientists at the U.S. Navy and Texas A&M University to help her scour the world for the exact phage that could target Tom's infection.
Steffanie Strathdee
00:08:06
When I realized, my God, there's 10 million, trillion, trillion pages on the planet, like, how am I going to find the right ones? And that was daunting, to say the least.
Stephanie knew the chances were slim, but she didn't care. Tom was dying, and she was on a mission to save his life.
Steffanie Strathdee
00:08:26
I thought, I have to leave no stone unturned. If he's going to die, I have to know that I did my very best.
Egypt 2015. A dream vacation for Stephanie and Tom that quickly turned into a nightmare.
Steffanie Strathdee
00:08:49
My husband was with me on vacation and we had this wonderful time. He looked like he was in good health and he had what I thought was food poisoning and it wasn't getting any better.
Tom had developed an antibiotic resistant infection that had overwhelmed his body.
Steffanie Strathdee
00:09:06
And unfortunately, the disease kept getting worse. The infection was spreading.
He's really close to dying. Yeah.
Steffanie Strathdee
00:09:12
Yeah. I had read about this thing called phage therapy. And when I asked my colleagues if we could try it, they said, Well, you know, if you can find phage that will match his bacterial isolate, we'll call the FDA and see if they'll give us permission to give it to him on a compassionate basis. We're not giving up either. So that's what we did.
Again, phages are viruses that eat bacteria. They can be found almost anywhere. In fact, this is where scientists found the right ones to help Tom. Holes of ships, barnyard sewage treatment plants all home to these naturally occurring viruses that could hopefully do what no modern medicine could. Finally, nine months after becoming sick, the Hail Mary came in the form of two purified phage cocktails.
Steffanie Strathdee
00:10:07
'After we injected phages into his bloodstream, even though he was in multi-stage organ failure, he woke up from his coma, lifted his head off the pillow and kissed his daughter's hand a couple of days later. Wow. Nobody could believe it.
Do I think Steffanie saved my life? Without a doubt. Stephanie saved my life. And that's really emotional for me to hear from people that I see from different countries that donated pages. The doctors took care of me, my family. They were by my side through the entire thing.
While Tom's case is extraordinary. Antibiotic resistant infections are not. They are far more common than you might think. In fact, in 2019, the United Nations estimated nearly 5 million deaths were associated with antimicrobial resistance, and that number is expected to double by 2050. With the hope of saving others, Stefani helped launch the Center for Innovative Phage Applications and Therapeutics. It's known as I Path. It's a lab focused on studying alternative treatments like phage therapy to fight antimicrobial resistant diseases. So far, she says, the demand has been overwhelming.
Steffanie Strathdee
00:11:30
We've had over 1700 requests for phage therapy since we opened our doors.
And when you get those calls, how optimistic are you that you could potentially help somebody?
Steffanie Strathdee
00:11:39
Well, you know, it came so well together for Tom that I really thought we could do this every single time. But that was naive. You know, if we had a phage library that had, you know, been stocked with phages that will kill the majority of bacteria that are affecting human health, we can source phage within a day or two and have it ready.
It's for that very reason. Biologist Graham Hatfull started collecting and analyzing cages at the University of Pittsburgh. But if you're not paying attention, you might miss it. It's hidden in plain sight, tucked away in an equipment room near his lab. And it is a treasure trove of phages. 23,000 of them, to be exact.
So this is perhaps one of the largest, maybe the largest collection of bacteriophages in the world.
In fact, with the help of faculty and students, Graham's lab has collected, isolated and now completely sequenced the genomes of more than 4000 pages. Decoding their DNA can help his team better understand each page and help them more easily find matches for specific infections. But again, do remember, there are trillions of pages out there still waiting to be discovered. So he and his colleagues turned to young minds, eager to learn and eager to explore. Pick your spot. Graham helped launch the C Phages program in 2008, which has encouraged now 45,000 students from 175 institutions around the globe to dig into the world of phages.
We want to develop programs where students could go and isolate new phages from the environment. They could study them, characterize them, name them.
From flowerbeds to sidewalks, dilapidated sheds. Students are learning that even a college campus is teeming with phages.
It's science all around us, and I think that it's extremely exciting that our next big discovery could just be from something as simple as a spoonful of dirt.
Their work appears to be paying off.
We've collected and written up and reported a set of 20 cases, the 11 out of the 20. We could determine favorable, clinical or microbiological outcomes. The patients got better in various different ways. And so even though that's not a magic bullet, that's 11 patients who were out of other options.
You may be wondering, what if this were you? What if this were someone you love? Someone in need of a Hail Mary. How do you know where to turn?
There was kind of a fullness in my left ear, and I couldn't hear quite as well. Out of that year.
It took Heather Kilar two years to even identify she had contracted an antibiotic resistant form of Mycobacterium abscesses in her ear. There was this towering stack of medical supplies in her home, which served as a constant reminder of how her condition not only impacted herself but also a young family.
One of the biggest things that we struggled with as a family was on communication because one of my ears wasn't working properly. So I had a lot of small kids at the time and their voices are really high. So I wouldn't pick up necessarily on what exactly they were saying.
She was given this extensive antibiotic regimen, meaning five different infusions a day, each one taking about an hour. But she saw little to no improvement.
We really realized that the drugs may work on paper. They may work in the petri dish, but they're not working for me.
After battling a slew of side effects with little to no results, Heather says she was done with antibiotics and began the daunting task of searching for alternatives. And like Stefanie, that search led her to phages. And Dr. Gina Suh.
Heather was on board from the very beginning. She was very excited about phage therapy. She has been a really great advocate for herself.
A biologist by training. Heather was cautiously optimistic that phages could be the answer she was desperately searching for. That is if they could locate the right one. Well, remember those phages in Graham's library? Well, two of them were a match, and shortly after researchers found and purified them, Heather received her personalized phage cocktail. First, the dose of saline is injected. Then come the phages. In the blink of an eye. It's all over.
Now that I've experienced no side effects from the phage treatment, where the traditional treatment had a lot of side effects that were difficult to deal with.
When I see patients who seem to be responding to phage therapy, there's really no greater joy. I mean, this is what I live for.
It took a village for Heather to receive her phages, and it took Tom a global team to find his. This sense of community and the connectedness with it is proving to be essential to phage success.
We clearly think that investigating, discovering, characterizing phages is a global rather than a local problem.
So where does the international phage community go from here? For almost 100 years, we have used antibiotics to fight infections in not only humans, but in plants and animals as well. But their overuse has contributed to a deadly rise of antibiotic resistant infections, and it's become one of the top global health threats we face today. Of course, the key to fighting it is to curb that overuse, whether that's in our hospitals or even our food supply. In the meantime, there should be this acknowledgment that tools exist all around us to also help in that fight.
Vorrapon Chaikeeratisak
00:17:46
So due to the high biodiversity of Thailand, we believe that there are a lot of bacteriophages that reside in our nature.
Vorrapon Chaikeeratisak is an assistant professor of biochemistry at Chulalongkorn University in Bangkok, Thailand. Along with his students, he is joining the global hunt for phages.
Vorrapon Chaikeeratisak
00:18:09
We are going to find whether or not the phage or the virus that in fact the bacteria exist in the nature.
The phages they are looking for could help prevent infections. And one of the country's main food exports, shrimp, in collaboration with the Thai Department of Fisheries water ponds lab analyze the bacteria that are causing disease in shrimp and we're able to find a phage to help protect these shrimp from infection.
Vorrapon Chaikeeratisak
00:18:37
What we found interesting more is that when we put the phage into the farm, the phage can colonize the gut system of the shrimp and therefore it could increase the immunity of the animals against the bacteria.
Now, to be clear, this research is still in its infancy, but are upon believes the results so far have been promising. In fact, he says the phage prevented about 40% of infected crustaceans in the study from dying. The bigger picture is that this could lead to using fewer antibiotics in our food supply, which is especially critical because the US Centers for Disease Control and Prevention estimated several years ago that 20% of all drug resistant infections in the United States actually come from the food we eat.
Vorrapon Chaikeeratisak
00:19:28
Speech therapy is one of the alternative tools that can be used to help Farmer instead of using the antibiotic.
It's unlikely that phages are going to replace antibiotics. Antibiotics are still going to have an important role. In fact, in Tom's draft, this case, his wife Stephanie, discovered how phages and antibiotics can work in tandem.
Steffanie Strathdee
00:19:52
We witnessed that, that, you know, the phage and the antibiotic were being used simultaneously to attack the bacteria.
Let me explain it like this. When a phage and an antibiotic team up against a bacteria, the bacteria often has to choose which one it ultimately wants to face. The way that a phage attacks a bacteria is typically by attaching to its capsule, which is like a protective shell. So the bacteria might choose to shed that shell in order to avoid a phage attack. But then that makes it more vulnerable to antibiotics. It's almost like the phage is acting like a decoy.
Steffanie Strathdee
00:20:31
This whole idea of being able to use phage in conjunction with antibiotics is a game changer in the field, either even on its own.
Phages will allow us to use fewer antibiotics. So if we can use those together, we can use our antibiotics in a more judicious way.
It's a sign phages could be the missing puzzle piece. Scientists have been searching for in the fight against antimicrobial resistance.
Ultimately, the goal would be to have such a deep understanding of those phage genome sequences and the bacterial sequences that you could simply use to predict which features you're going to use for which particular infection.
I think we are all in this because we recognize this responsibility almost to come up with another solution because we owe it to the next generation. We want to help.
Where do you see this going? If I come talk to you in ten years, what do you think phage therapy is going to be like in terms of acceptance?
Steffanie Strathdee
00:21:37
Well, ten years from now, I would think that a lot of clinical trials will have been done. I believe that they're going to show efficacy. But, you know, I'm a scientist. I want to see the data. Right. I don't want to rush to make a judgment without those trials being done.
Only time will tell. But thanks to phages, Tom and Stephanie now have more of that time.
Kind of feels like it's the reason we're here on this earth. Yeah. And to have that kind of a privilege is astounding. This is what is going to be remembered. Yeah. This is what's going to make a big difference.
Steffanie Strathdee
00:22:12
To your legacy.
Steffanie Strathdee
00:22:16
Our legacy.
A legacy born of this Mother Earth providing medicines for so much of what ails us. If we just take the time to stop, listen and look. And I'm going to be right back to answer one of your questions for our On Call segment, which is quickly becoming one of my favorite parts of the podcast. This question is going to be about what it means to be in a flow state. Okay. It's time to reach into the mailbag. And this week's voice mail comes from Eric in Santa Cruz.
Hi. My name's Eric Decker. And it struck me that an interesting episode in the future would be focusing in on the psychology of Flo and Flo State, which is where I find my happiness, particularly when I'm skiing and mountain biking.
'Okay, Eric, you bring up a good point. Skiing, mountain biking, surfing. When done with a certain level of competence and confidence can transport you into a state of flow. Some people refer to it as being in the zone. Now, what does that mean exactly? You can think of it as being fully immersed in the activity, be it a sport or an instrument, even solving a math problem. Reading. You lose almost all sense of time in what is going on around you. Mihaly Csikszentmihalyi. He's the Hungarian psychologist who is credited with popularizing the concept of flow. And he described it like this, being completely involved in an activity for its own sake. The ego falls away. Time flies. Every action movement in thought follows inevitably from the previous one. Like playing jazz. Your whole being is involved and you're using your skills to the utmost. As you know, I'm a brain surgeon, a neurosurgeon. So let me explain it like this. During flow. The prefrontal cortex, that's the front part of your brain. The part of the brain that's responsible for our conscious state of mind. Think of that as being downregulated taken offline a bit, leading to a loss of self-consciousness and a quieting of the inner critic. Time becomes distorted. Researchers theorize more parts of the brain start to communicate freely and be creative. There's a lot going on in the brain during that flow state. And to get in the flow state and stay in the flow state, you need to be engaged in an activity that is sufficiently challenging but not too hard that you struggle and become overwhelmed. Not too easy that you quickly become bored and something that you get instant feedback on that lets you adjust and optimize your actions. When you're there, you kind of know it and it's amazing. So knowing all that, get out there and go with the flow. Chase life.
