Science Friday - Antibiotic Resistance, Space Launches and the Environment, Phage Therapy. May 5, 2023, Part 2

Episode Date: May 5, 2023

SpaceX Explosion Damages Environment Around Launch Site Last Thursday, SpaceX’s South Texas facility was awash in noise and fire, as crowds gathered in South Padre Island and Port Isabel to watch Starship’s first orbital launch. It was the largest and most powerful rocket ever made, standing at around 400 feet tall. Four minutes into the launch, SpaceX detonated the rocket after the SuperHeavy booster failed to separate from the Starship as planned. The launch destroyed the company’s launch pad, spreading concrete up to three quarters of a mile away. Cameras left by YouTubers were either knocked down or destroyed in the rumble, along with some of the fence surrounding the launch pad’s road-facing property. To read the rest, visit sciencefriday.com.   The Private Space Race Takes A Toll On Planet Earth After the SpaceX explosion last month, debris wasn’t the only thing on the minds of Science Friday listeners. The following messages arrived in our inbox after we reported on 3-D printed rockets in March. It was interesting to hear you discuss 7 space launches in 5 days, and then just moments later the fact that we’re not on track to reduce carbon emissions. My understanding is that rocket launches release huge amounts of carbon and other greenhouse gases. Story idea?—@RevBobIerien, Twitter Also regarding the 3-D rockets there wasn’t any concern made for space pollution was there? I may have tuned out unhappily before the end. —Juanita H, email How much carbon do rockets contribute to global warming? —Robert C, email Very disappointing to hear the report of new “cheaper” 3D-printed rockets are available so that, like fast food pods and big gulps, we can now drop even more cheap **** into the ocean. And, *immediately* following a story about the new report on climate change, what exactly is the carbon footprint resulting from the ability of more people to more cheaply fire rockets into space? —David M, email Carbon isn’t the big pollutant that comes from spaceflight, says Dr. Eloise Marais, associate professor in physical geography at University College London. Instead, black carbon or soot particles are generated and released directly into the atmosphere, alongside reactive nitrogen and nitrogen oxides. Dr. Marais joins Ira to talk about how much of an impact increased rocket launches could have on the atmosphere, and how that compares to the auto industry.    How To Combat The Antibiotic Resistance Crisis For years scientists have been ringing alarm bells about a global antibiotic resistance crisis. Now hospitals and healthcare facilities face the consequences: In the United States, there are 2.8 million antimicrobial-resistant infections every year, and more than 35,000 people die from these infections. Bacteria naturally try to outsmart the drugs designed to kill them, which causes treatments to become ineffective over time. While new antibiotics are made to respond to these resistant strains, the bacteria continue to evolve—creating a constant, and costly, cycle. There’s a number of added factors driving the crisis, including antibiotic use in livestock and the general overprescription of antibiotics. About 1 in 3 antibiotic prescriptions in outpatient settings like urgent care or emergency departments are unnecessary. Scientists are struggling to keep up with the need to replace antibiotics that no longer work. It’s a never ending game of catch up. Ira discusses some of the possible solutions to this vexing problem and takes listener questions with Dr. Victor Nizet, faculty lead of the Collaborative to Halt Antibiotic-Resistant Microbes at the University of California San Diego and Dr. Eddie Stenehjem, executive vice chair of medicine at the University of Colorado.   Are Phages A New Page In Medicine? One of the many possible solutions to the global antibiotic resistance crisis is an old idea that’s new again—bacteriophages, or phages for short. Phages are viruses that exist solely to kill bacteria and are abundant in nature. While scientists first discovered phages’ ability to treat bacterial infections about a century ago, there’s been little interest in turning them into a treatment for patients with antibiotic resistant infections—until recently. Ira talks with Dr. Graham Hatfull, professor of biotechnology at the University of Pittsburgh about the latest in phage science.   Transcripts for each segment will be available the week after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Flato, and now it's time to check in on the state of science. This is KERNNO. St. Louis Public Radio News. Iowa Public Radio News. Local science stories of national significance. Last month, crowds gathered in southeast Texas to watch SpaceX launch a new rocket from its Bocca launch pad on the coast of the Gulf of Mexico. It was a test flight of the largest and most powerful rocket ever built. about 400 feet tall, and it was to be its first orbital launch attempt.

But as often happens in the rocket business, things did not go as planned. The uncrewed rocket exploded shortly after launch, a very common occurrence in the history of rocket science. The environmental impact of rocket explosions, though, has not always been front and center, but this one has been reported by my next guest. Gage Davila, reporter for Texas Public Radio, based in Port Isabel, Texas. Welcome to Science Friday. Thank you so much. I appreciate it.

Now, you live near where the rocket exploded, right? Did the explosion impact the area? What does it look like right now? Well, here in Port Isabel, immediately after the launch, there was a plume cloud that made its way to the city and a little north of it that clouded the area in dust that was made of sand, soil, and pulverized concrete. But we've had some storms here in the last couple of weeks,

So most of it is washed away. I've kept some of it, and I'm looking to get it tested. And in terms of Bocchika Beach, there was concrete all over the launch pad, spread about a mile around in all directions. And some of that concrete and pieces of the launch tower, which were metal, of course, were found in sensitive algal mud flats where shorebirds feed, and those flats can take up to a decade to heal. That's what I wanted to ask you next.

Tell us about this protected ecosystem there. So SpaceX's facility is essentially surrounded by mud flats of varying degrees of sensitivity. Some of them are just mud. Some of them are just sand. But others have a thin layer of algae and biofilm on top of them. And they're extremely sensitive to the degree that in previous launches that SpaceX has had, whenever debris had landed on these layers of algae, the marks are still there all these years later because it takes so long for them to heal.

And shorebirds eat off of these pieces of biofilm along with crabs and other vertebrate of that nature. And, of course, it's a area where migratory shorebirds come in and rest as they make their way towards Mexico and Central America. Are there any environmental regulations that SpaceX or anybody would have to follow? The FAA, which is the Federal Aviation Administration, requires SpaceX to do 75 mitigating actions to lessen the impacts of starships launches. Some of these include protecting water sources, watching noise and lighting levels, beach cleanups quarterly, you know, no beach closures on holiday, et cetera. And they were required to do these as part of SpaceX's launch license. Did it fail to follow these regulations? Well, I think SpaceX underestimated.

how this launch would turn out in terms of the launch pad being destroyed and how much damage there was. So I don't know if it's really a question of them following the mitigations, but more on how SpaceX had the chance to build better launch infrastructure that could have prevented the damage, but chose not to. I spoke to an environmental compliance specialist named Eric Resch, who also questions SpaceX's operation. It sure seemed like the decision to not do these very basic channels or flame protection or systems you see everywhere else was a matter of convenience. What is SpaceX's reaction to all of this? So recently Elon Musk said that the launch didn't cause any, quote, meaningful damage to the area.

Maybe it's not meaningful to him, but it does matter to the people who live here and those who study in the environment here. It's also just not true. Each launch compounds the damage inflicted from the last. Justin LeClair, who is a conservation biologist with the Coastal Bend Bayes and Estuaries program, explained it this way. If these major disturbances in addition to actual damage to the habitat just happen consistently every month, every week, birds and other wildlife are not likely to use that habitat. Early this week, environmental groups sued the FAA over SpaceX's launch license. What are the details there? What's going on?

So the groups involved in the lawsuit are essentially saying that the FAA has let SpaceX environmentally regulate itself. And this is because the FAA had initially planned a more thorough environmental analysis that would have taken years to complete, but instead deferred to SpaceX on what process it wanted to go through. SpaceX, of course, chose the process that took the least amount of time. So the claim is that the FAA through political pressure from SpaceX moved along the process without a true. true look at the environmental impact the launches would have had on the area. Well, could we see a large or a long delay then in any next test flight? Possibly because the FAA has launched an investigation into the launch, which could take a few months to complete, but locally, I don't think so, because local leadership has been noticeably

quiet. They have taken a step back from their usual voicing of support for SpaceX in the last couple months. And with this launch going the way that it has, I don't think it's a coincidence that we haven't seen them respond to it. And of course, the federal government can always overrule any kind of FAA decision as part of national security because they need SpaceX to get to the moon. Right. That's a big question in this is the fact that they are expecting SpaceX to do something within, I believe it's 2025 in order to get closer to those huge. human-oriented moon missions, but the way that it's going now, they seem to be just going through roadblock after roadblock because of the missteps that they take. Well, Gage, thank you for

reporting for us. Thank you so much. I appreciate it. Gage, W.L. Reporter for Texas Public Radio, based in Port Isabel, Texas. Debris isn't the only environmental consequence of space flight. Air pollution comes from rockets leaving and reentering Earth with private companies launch rockets more often than ever before for space exploration or tourism, how much pollution is being added to our atmosphere and is it significant? Joining me to evaluate this question is Dr. Eloise Moray, Associate Professor in Physical Geography at University College, London in the UK. Welcome to Science Friday.

Hi, Ira. Great to be on your show. Thank you. You're welcome. We got a lot of questions from listeners recently. Robert, David Bob, all writing in to ask how much carbon comes from rocket launches, and I assume that they mean CO2, the greenhouse gas. Can you answer that question for them? Yeah, not much, especially in comparison to the CO2 that's emitted from our sources on Earth. So burning of fossil fuels

like coal and natural gas, vehicles, ships, a whole host of oil. sources that contribute to CO2 on the ground. The carbon footprint from rocket launches is quite low in comparison. What other pollutants are coming from the space fly? Yeah, the pollutants that we're most concerned for in terms of their environmental influence are soot or black carbon. These are tiny black particles that come from propellants that have carbon in their chemical structure. And these Soot particles, because they're dark, they're very efficient at absorbing the sun's radiation, and in the process, they heat the surrounding atmosphere. Then there's also reactive gases that are released that are injected directly into the stratospheric layer,

the layer that's protecting us from harmful UV radiation, and many of them react with ozone, essentially depleting it, so thinning that layer that's protecting us from the sun's rays. Is it possible to know just how much pollution is coming from rockets? We can calculate roughly what major pollutants are coming from rockets. We have information about the types of propellants that are used. They undergo combustion. And in this combustion process, they typically produce a host of pollutants. And we have some information about the amount of these pollutants that are produced per kilogram.

of propellant burned. But of course, with all of these calculations, it's not a precise estimate. It's a good enough estimate for us to be able to assess the influence on the environment. Are there factors that change just how much pollution is occurring during a launch or a re-entry? Yeah, it's mostly to do with the kind of propellant and the amount of propellant that's being burnt for the launch process. And then for the re-entry process, a bit of a combination of what's being burnt and how fast it's moving through the atmosphere as it burns. Private companies like SpaceX are able to make and launch rockets at a speed we haven't seen before. Do you have?

Do you have specific concerns about how these companies operate? Yeah, especially if Elon Musk's ambition of having three launches a day, and that's every day, in the year, and that's just one company. That's about a thousand launches per year, and we haven't quite hit the 200 launches per year mark. So this will be a substantial increase in the amount of rockets that are launched, and then the amount of pollutants that are produced as well. And unfortunately, for something like soot particles, the rockets have an overwhelmingly larger influence on climate than the soot particles that are produced near the surface of the earth because the soot stays up in the higher layers of the atmosphere for so much longer.

The longer it's there, the greater the effect. But how much does this really compare to the auto industry or power companies burning coal and oil? We conducted a study where we focused on 2019 rocket launches, and this is before the exponential growth in the number of rockets being launched. And in that study, we estimated that the amount of soot that's produced from rockets is very small in comparison to all other anthropogenic sources representing something like 0.01%, really, really small. But the climate effect in comparison to the other surface sources is 3%.

So considerably larger than the amount of emissions. And the implication there is that we don't need to grow the rocket industry. as much as, say, the number of flights we have to be able to have a similar impact. Well, that's very interesting. And thank you for taking time to be with us today. Sure. It was great chatting to you. Dr. Iloes-Marie, Associate Professor in Physical Geography at University College London in the UK. This is Science Friday. I'm Ira Flato. You might remember headlines from a few years ago, ringing alarm bells about a global antibiotic resistance crisis.

The issue might not exactly be front and center while we were busy focusing on combating COVID-19, but the bacteria did not take a COVID break. These microbes kept working hard to outsmart the antibiotics designed to kill them. There's a number of factors driving the crisis, including antibiotic use in livestock, the general over-prescription of antibiotics by physicians. In fact, about one in three antibiotic prescriptions in outpatient settings. like urgent care or emergency departments, one in three are unnecessary. And scientists can't keep up with developing new treatments needed to compensate for antibiotics

that no longer work. It's a big game of catch-up. In the U.S., there are almost 3 million antimicrobial resistant infections every year, and more than 35,000 people die as a result. Joining me now to talk about some possible solutions to this vexing problem and answer your questions about antibiotic resistance are my guests. Let me introduce them now. Dr. Victor Nezzi, excuse me, Dr. Victor Nezze, Professor of Pediatrics and Pharmaceutical Science, the Faculty Leader of the Collaborative to Halt Antibiotic Resistant Microbes. That's at UC San Diego, San Diego, based in San Diego, California. And Dr. Eddie Stenium, Executive Vice-Bist. Chair of Medicine at the University of Colorado based in Aurora, Colorado. Welcome to Science Friday. Good afternoon, Ira. Thank you for dedicating time. Nice to have you. And we want to hear from our listeners. What are your biggest questions about antibiotic resistance? Have you noticed a change in

prescribing habits at the doctor's office? Have you ever suspected you'd been given an antibiotic for a viral infection? Our number 844-825-8-4-7-24-8-25-8-8-4-7.4-7.7.7.4-7. site talk, or you can tweet us at SciFRI. Let me begin with you, Dr. Nez. To start off, can you give us an overview of how antibiotic resistance occurs in the body? Well, bacteria, when they're exposed to a chemical antibiotic, can either be susceptible, meaning they're killed, or their growth is halted, or resistant, meaning they survive the exposure. exposing them to an antibiotic is a life or death selective pressure.

And by Darwinian evolution, mutations occur in the bacterial population that can lead to a change in the bacteria. So it no longer binds the antibiotic, inactivates the antibiotic. So the drug doesn't work in the humans. So Dr. Nizet, how does taking repeated rounds of antibiotics fit into antibiotic resistance? Well, it's a cumulative exposure. Bacteria are very small. They're replicating every 30 minutes, so they have a tremendous mutation capacity, each exposure to antibiotics, especially if the bacteria are not completely eradicated, gives them an opportunity to gain strength and expand their resistance. This can spread in the communities.

and create significant public health problems. So it's sort of a survival of the fittest among the microbes, the stronger ones, stay alive while you knock off the weaker ones? Exactly. I don't think there's a better present example of Darwinian evolution. You can do it right in front of your eyes in the laboratory. As I outlined in the introduction, there are several factors driving the antibiotic resistance crisis. Do we know how big a role each factor is contributing to the issues?

So let me ask each one of you, Dr. Stanyam? Yeah, it's a great question. And the answer is we don't know. There's a lot at play in terms of what is deriving resistance. It's antibiotic use in the hospital and its subsequent transmission of resistant pathogen. It's antibiotic use in the outpatient setting. all those emergency department, urgent care, primary care visits that receive antibiotics, it's antibiotics in livestock and subsequent development of resistance in livestock.

And so it's all of these things taken together that is really driving the crisis that we're in. Dr. Nisei? Yes, and I think another point is that historically we've relied on a single class of medicines as antibiotics, these chemicals that have a direct action on the bacteria. And I believe that we've become complacent and maybe not had as much innovation in the field of antibiotic medicine that is necessary to most effectively treat diseases.

And maybe we can take some lessons from the advances in cancer therapy and other fields where they've harnessed the power of the immune system, develop more targeted rather than broad-spectrum therapies. And with a bigger arsenal of tools for the doctors, we might derive better patient outcomes and less selection for resistance. So you're focused on creating a more holistic approach to treating infection.

Yeah. If you think about it, having an infection is not just that the bacteria had the potential to produce disease, but that the patient's immune system dropped the ball that day to allow the bacteria to spread deeper in the body. And what we're discovering is that you might think of alternatives to chemical antibiotics that kill the bacteria or poison the bacteria. Rather, you might understand the tools the bacteria is using to cause disease, we call these virulence factors,

and try to disarm the bacteria. An advantage of this kind of therapy is it would be specific for the individual pathogen by targeting its specific virulence factor and not have the adverse effects on all the beneficial bacteria that make up our human microbiome, and it would also reduce the selective pressure for resistance on different bacteria in the body. You've also done some research about how antibiotics are developed in the lab in the petri dish. Why is the standard operating procedures for developing antibiotics falling apart? Is the petri dish not good enough representative of how antibiotics work in the body?

Yeah, if you think about it, the testing that we do to determine whether an antibiotic is effective, whether the bacteria is susceptible or resistant, is done in a clinical laboratory on media that is designed to support the growth of the bacteria outside the body. It's basically brief broth and seaweed auger really doesn't resemble the conditions inside the body. And what we found is that if you test the very same antibiotics and bacteria under conditions that are more representative of the body that have the same salt conditions and pH that are present in body fluids, you get different results, and we may be inadvertently neglecting or discounting certain antibiotic activities, ruling them out based on the laboratory test when they're effective in the body.

Plus, this testing doesn't have any element of the immune system, and there's actually many antibiotics that collaborate with or synergize. They change the bacteria to render it susceptible to the immune system. And in fact, in this arena, we can repurpose many medicines that are used for other conditions, like statins, cholesterol-lowering drugs, anti-platelet drugs, anemia drugs, and find that they change the host-pathogen interaction, so to speak, to the advantage of the host and have therapeutic benefit in clearing infections. You're saying they change the microbiome in our...

That's another great idea. Rather than damaging the microbiome, we can support the microbiome. And there's actually probiotic treatments that have been shown to benefit, fortify the barrier. Remember, all of us is not just a single life form. We're really the mayor of a large community of beneficial microbes that live on or inside our bodies. And antibiotics damage the integrity and diversity of this have led to increase. rates of obesity and autoimmune disease and allergy, we should fortify that, look for therapies that don't disturb the microbiome, targeted therapies. I love that, I love that description being the mayor of large microbiome. Dr. Stenium, I want to talk a bit about the overprescription issue. We have known about this for a while, haven't, haven't we? I mean, we've been talking about

it for decades here on this program. Why are doctors still overprescribing? Yeah, it is fascinating that we have been having this discussion for decades. We've known that a large majority of, not a large majority, but a large amount of antibiotics that are given in the outpatient setting are just inappropriate. They are either not needed or if they are appropriate, many times they're given at the wrong dose or for the wrong duration, say 10 days when five days would have been fine. And I think we're realizing that this is a much more complex issue than what we made it out to be. For years, it was, oh, we just need to educate our physicians and our

nurse practitioners and physicians assistants. They just need to do better. We'll just do more education. And we find that it's much more complicated than that. And that it's not just sheer education. We have to deal with the newfound, you know, respect of patient satisfaction and patient pressure. We need to think about the time constraints that we're putting on our clinicians in busy urgent cares, in ED where some clinicians feel that it's just quicker to be able to give an antibiotic move on to that next visit. We need to be able to manage all of these things and be able to design systems where clinicians feel they can take the time and explain to the patient why an antibiotic is not required. And it's not.

going to be beneficial and in many respects and many times it can be actually harmful. We have to be able to give them that space to do that where they're not worried about having to get to that next patient even quicker. We need to be able to provide them tools to make sure that they're certain of their diagnoses. And I think we saw this during the COVID pandemic, they'd be able to give clinicians diagnostic tools to be able to put a label to the condition that the patient has. you have COVID or you have influenza to be able to take comfort in knowing what the patient has instead of just saying, oh, it's a virus, it's going to run its course. So I think it's a much more complex problem.

And just to Dr. Nasei's point is we need to continue to evolve in the diagnostic space, the therapeutic space, the behavioral and implementation science space to really move the needle on outpatient antibiotic prescribing, because it really hasn't moved, at least in the adult world, for decades. Well, you also found that doctors understood antibiotic over-prescription to be an issue, but that it was the other doctors, not themselves, right? What happened when you provided doctors with their own prescription rates? Right, and so Intermountain Healthcare where I worked just most recently, we were able to take

and to a large initiative in our urgent care network, which is a network of 38 urgent cares. And we were able to successfully reduce respiratory antibiotic prescribing significantly from 48 percent down to about 30 percent. And part of that was being able to provide the clinicians their antibiotic prescribing rates and allow them to see that and allow them to see other people's data as well. We did this an incredibly transparent matter where they could see their prescribing behavior and also their peers in their clinics or across the system. And in many cases where they thought, oh, I'm just doing it better when we were able to show them their data and allow them to compare it to peers and allow them to talk with peers that do

it better to learn from them. How do they have these conversations with patients? We saw people move in the right direction in terms of antibiotic prescribing. and in the end, not too many people were very upset about showing their data to the rest of their colleagues because they could learn from them. Very interesting. This is Science Friday from WNIC Studios. We're talking about antibiotic resistance. Let's say if we can get a call in before the break.

Let's go to George, a new Bedford mass. Hi, George. George, are you there? Let me try hitting the button again. George, are you there? Yes, I am. Hi there, go ahead. All right.

I was wondering what the status of Mercer, the flesh eating bacteria that was rounding about in hospitals, et cetera. I haven't heard anything about it, and it's resistance to antibiotics lately. Gentlemen, who would like to tackle that one? I can speak from a scientific point of view. Go ahead. We certainly still have Mercer as one of the leading antibiotic-resistant checks. challenges. The rates are a little bit down from their peak, and a frightening specter of resistance to vancomycin, one of our last line antibiotics, seems to have not fully materialized. However,

patient outcomes in treatment with serious MRSA infections have kind of stalled. We see very high mortality in deep-seated infections like bacteremia and sepsis with staff, resistant and susceptible strains, which means we need better therapies. We also need a staff vaccine, which has been a real challenge for a long period of time. But it's in this arena where combination therapies, rapid diagnostics that let us know we're dealing with a metacillin-resistant MRSA strain quickly, combination drugs, therapeutic antibodies. You heard about monoclonal antibodies during COVID. A beautiful paper came out from the Victor Torres Lab at NYU, showing a multi-target antibiotic

or antibody that neutralizes the toxins that the bacteria makes and can lead to better outcomes in staff infection. So a lot of reason for optimism, but it's still a very prevalent leading threat. Dr. Stenium, is there one, you know, is Mercer the top problem now with endobiotic resistance? Yeah. As a practicing infectious disease physician, I can tell. you MRSA or MRSA is alive and well. It is something we treat every day in the hospital. And it certainly causes very significant morbidity and mortality in our patient population. It's one bacteria that we have high concern for and agree that we need better therapeutics for this particular severe infection.

But other bacteria, such as gram-negative bacteria, these are bacteria that predominant live in our gut. They cause urinary track infections, control us bloodstream infections, are really seeing an increase in drug resistance and can cause very significant mortality rates in our patients and are really the concern of clinicians that are treating these patients in the hospitals. All right, we have to take a short break, and when we come back, we're going to continue our conversation about antibiotic resistance. If you'd like to join us, please, our number, 844-8255-8-4-Sight-Talk. What would you like to talk about?

You make the call, but only if you make the call. 844-724-8-255 or tweet us at SciFri. Stay with us. We'll be right back. This is Science Friday. I'm Ira Flato. We're continuing our conversation about the global antimicrobial resistance crisis and its solutions with my guest, Dr. Victor Nizze,

Professor of Pediatrics and Pharmaceutical Science. and faculty lead of collaborative to halt antibiotic-resistant microbes that's at UC San Diego, and Dr. Eddie Steniam, Executive Vice Chair of Medicine, University of Colorado, based in Aurora, Colorado. Our number 844-8255. Let's see how many calls we can get in before we have to go. Catherine in Ethica, New York, hi there. Hi there, how are you? Hi, go ahead.

My name is Catherine. I am a registered nurse. My specialty is end-of-life care, both hospice and palliative care. And it's been very disturbing to us as a profession to recently have patients that we are unable to keep comfortable because of the extent to which the FDA and other organizations have throttled down on opioids. I respect that the thought is that this will curb accidental overdoses. However, that has not borne out in reality. The heroin fentanyl combinations out on the street seem to be, and in fact are a much more deadly combination.

So it surprises. I do appreciate the efforts, these programs that are trying to bring awareness to prescribers about antibiotic misuse, but it surprises me that the FDA has not weighed in more heavily on the matter of overuse of antibiotics leading to antibiotic resistance. For example, there are many broad-spectrum antibiotics that can be obtained without prescription that are intended for veterinary use. I wonder if your guests have any thoughts about why the FDA is not engaging in a more robust response to the issue of over availability of antibiotics. Thanks for your call. Dr. Stenium, can you tackle that?

Yeah, Catherine, it's a great question. And I would say, you know, the FDA is in the business of approving medications for use in humans. and we have had very significant progress in curbing antibiotic misuse and the inpatient setting and the hospital setting because of some key regulations that have come through both CMS and the Joint Commission. These bodies oversee and regulate hospitals. And what we've seen is a very significant increase in hospital-based antibiotic stewardship programs, which allow clinicians to better utilize antibiotics, we've seen an increase in these programs because of the advent of CMS and joint commission regulation. So we do have some policy-based guidance on the inpatient side that has improved antibiotic prescribing.

I think to your point, though, is we don't have any policies on the outpatient side to govern and oversee antibiotic prescribing. And there's work looking at incorporating payers into this discussion. and how can we incentivize clinicians through the payer arm to better prescribe antibiotics? And I think as we move to a more value-based care model of payment structure, antibiotic overuse is going to be very front and center. We know that as antibiotic resistance go up, so does cost of health care. Let me see if I can get one more call. And Lisa in Yuba City, California.

Hi, Lisa. Hello, yes. We know that antibiotics are found in. most every water system. And we know that when these antibiotics and other drugs co-mingle together, they morph into various complications. But what we don't know is how these complications are going to accept us in the future. How significant is that? Yeah, yeah. Good question. All can take a crack at it, Victor. So, yes, this is, environmental release and exposure of antibiotics.

We highlighted extensive use in agriculture as one source, but also you can find it in the effluent of the factories where they're making the antibiotics and levels of antibiotic-resistant bacteria are present in countries like, India and China where they are developing the antibiotics and there's... Don't we flush them down the toilet ourselves? And we take them? Exactly.

And we flush them down the toilet ourselves. So wastewater detection and its sensitivity and throughput made a big impact on our management and staying one step ahead of COVID epidemiology and the emergence of variants. This was led at our university by Rob Knight as a model that was adopted elsewhere. And I think we can take the infrastructure that we've developed there and focus it on the key antibiotic-resistant organisms and genes to get a good barometer, not just from sick patients in the hospital, but the presence of the genes in the community to guide, our prescription practices and target our interventions. Are you hopeful for antibiotic resistance and antibiotics? I think, you know, it's been said that infectious disease is the only specialty in medicine

where we can reliably count on the drugs getting less effective over time and also new diseases emerging. We don't have a new high blood pressure disease and we don't expect our blood pressure medicines to lose effectiveness over time. But I do believe that following the model that we've seen in other fields of medicine, towards personalized medicine, towards immunotherapy, maybe the pressure of this epidemic and some creative economic tools to boost antibiotic research investment like the Carbex Accelerator or incentivized companies post-market, like the Paster Act. I'm going to have to leave it right there.

We're running out of time. We've reached the end of the segment with Dr. Victor Nuzzi and Dr. Eddie Stenium. Thank you both for taking time to be with us today. Thank you, Ira. Thanks for having us. I'm Ira Flato. This is Science Friday from WNIC Studios. I want to end the hour focusing on a very intriguing possible solution to the global antibiotic resistance crisis,

and it's an old solution that's, well, new again. It involves using bacteriophages to treat infections. Now, a phage is a virus that exists solely to kill bacteria, bacteriophages, and they are abundant in nature, a gazillion of them everywhere. And while scientists, first discovered phage's ability to treat bacterial infections, oh, about a century ago, the advent of antibiotics around World War II put a damper on phage research. There's been little investment to turn phage medicine into treatments for patients with antibiotic-resistant infections. Until recently, joining me now to talk more about phage science is my guest, Dr. Graham Hatful, Professor of Biotechnology at the University of Pittsburgh, of course, based in Pittsburgh, Pennsylvania.

Welcome to Science Friday. Hi, Ira. Great to be here. You've been researching phages since, what, 1988, some 35 years? What prompted you to get into this? Sounds like a long time, isn't it? For serendipity, really, I was interested in another topic entirely, really. I was interested in some ways in which systems do DNA.

recombination and heard about a phage system that we might like to investigate, started digging deeper, getting DNA sequences and doing genomics, and realized that there was a whole new world out there that we hadn't really even imagined unearthing. And we've been delving into that ever since. It's funny, that first pun of this segment unearthing, because that's where you find the phages, don't you? Absolutely. Well, phages are everywhere. And certainly, in earth and soil and compost is a place that we and our students, many of our students, have gone and searched for phages successfully finding them that infect some of the bacteria that we're interested in. But they are everywhere. And so wherever you go, you can usually

find some phages. Let's talk about the word you use success because you have been successful in treating patients with phages, treating their antibiotic-resistant illnesses successfully. Tell us about that? Well, we were first contacted by a colleague that I know from London about five years ago when they had a couple of patients that had infections that they just couldn't resolve with antibiotics. Patients were very poorly, and after some conversations, they sent us a couple of bacterial strains. We have a large collection of bacteriophages that were isolated on similar strains, and so we set about a search to see if any of the phages in our collection might be useful potentially for a therapeutic intervention for those patients. And although it took a lot of effort, a lot of screening

and some engineering, we're able to come up with a cocktail of three phages that we thought might be a good candidate therapy. They were administered after all of the appropriate regulatory approvals, et cetera. And they were administered on a compassionate use basis. And I think the patient clearly did very well in terms of being able to resolve much of the infection, at least, and to get back to the semblance of a normal life. Amira Flato, and this is Science Friday from WNYC Studios. And how many people have you treated in total successfully? Well, we've treated a total of about 35 now or so. Some of those are ongoing, but we've written up and reported some details about a consecutive series of 20 cases, and there are definitely successes there, but not universally so.

And so, about of those 20 cases, five, we couldn't really easily adjudicate for various complex clinical circumstances. Of the other 15, four, we didn't obviously see any improvements in the infections. Of the other 11, we saw favorable outcomes, either clinical outcomes or microbiological outcomes. We take that as a very encouraging sign, especially as, you know, these are patients who are very sick, have many difficult and complicated clinical manifestations. And so it's not universal success, but I think it's an indication that maybe this is worthwhile looking into in greater detail. And how would you look into it in greater detail? All of these cases that we've been involved in are on a compassionate use basis, so individual cases. They're essentially anecdotes.

And if you have a series of them, you can certainly see some patterns that emerge, but nonetheless, they're anecdotes. And that's really not good enough for us. What we'd like to see are clinical trials where you can do it in a controlled, in a blinded way, and try to get real data, real insights on the variables that influence whether they work or not, the safety, the efficacy, routes of administration, dosage, all of that are basically just guesses at the moment. So we'd like to do the science, the clinical trials, and get some answers. And what is stopping you from doing that? There's still a lot that we don't know. And one of the underlying complications, especially for the types of bacteria that we're interested in, is that if you look at the

clinical isolates of those strains from different patients. They all behave very differently when we try to kill them with phages. Some of the phages kill some strains, but not others. And there's a great deal of specificity of the phages for individual patient isolates. So we don't have, you know, a cocktail, a vial of medicines that we could use in a clinical trial for all the patients that would enroll because we don't have phages that are going to address all of the clinical isters. So this question of specificity, what determines it, is really a core question that we've got to get some answers to. Yeah.

So it's a matter of finding the right phage for the right infection? Much of it is really like doing personalized medicine, finding phages that might work for a particular individual patient. And we've been sort of really interested and delighted to do that from a compassionate use basis to see if we can provide some help for patients with those infections. It just is a real complication when you want to do a clinical trial. You actually run a program called C-phages, where undergraduate students actually hunt for phages, which then get sequenced and entered into your giant database. Where did the students find these phages? Anywhere that students want to live.

look, as you can imagine, there's a lot of opportunities there. We started developing phage discovery programs that students could actively be involved in bacteriophage discovery and genomic analysis, well, back in 2002, really. And we developed those programs in Pittsburgh, and then schools, institutions, community colleges can participate, essentially run a course where we train faculty need to teach that course and to provide the resources and the databases, all the common entities that they need to do that. And then students over a course of usually two terms, usually as first year students, go and discover new phages. They isolate them, they characterize

them, they name them, look at the genomes and add them to the database. And some of those are ones that we're using for therapies and patients. Right. Well, you say that one of the problems with the phages is that they're so specific for an infection. Is it possible to genetically engineer them a bit so that they, you know, might be a little more broadly used? Yeah, we think that's part of the solution. One of the things that makes the therapeutic use of phages kind of a bit more exciting than it might have been a few years ago is the ability to be able to engineer the phages a lot more readily to maybe add genes that will make them act better or more efficiently or to change. Or to change. change them in ways in which we can overcome that problem of specificity to expand the numbers

of types of strains that they infect. And so that's something that we're actively engaged in. And it's a step by step and relatively slow process. But I think that engineering and just doing the underlying genetics on some of these phages is going to provide some solutions to using these for broader therapeutics. Well, Dr. Hathfield, don't be a stranger. Come back. and tell us about your advances. Well, thank you. Always happy to talk about phages. Every day, every way. Dr. Graham Hatful, professor of biotechnology,

at the University of Pittsburgh, of course, in Pittsburgh, Pennsylvania. And if you listen to Science Friday, a lot, we've been talking about phages for, what, three decades or more, and we'll continue to follow them because they're really an interesting topic. And that's about all the time we have. If you missed any part of this program, or you'd like to hear it again, subscribe to our podcast. Yes, or ask your smart speaker to play Science Friday.

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We'll see you next week. I'm Ira Flato.