METTA SPENCER: Today I’m talking with Dr. Laura Kahn, an expert on anti-microbial resistance. She knows about bacteria, and she’s into viruses these days with a new book coming out, called One Health and the Politics of COVID-19. That sounds significant, because probably more people died of stupid politicians convincing them to do stupid things than from medical inadequacy.
KAHN: And politics was involved in the controversy about Covid’s origin. And then there’s the whole leadership aspect, which I’m just starting to investigate.
SPENCER: But today we’ll discuss an older issue – how we are becoming immune to the antibiotics that would have saved us if we hadn’t messed up. I think that’s the issue that your book was about, which is several years old now. Right? Remind me of that book’s title.
KAHN: It was published in 2016. One Health and the Politics of Antimicrobial Resistance. The material that it covered hasn’t really changed. And it’s not that you’ve developed immunity to the virus, it’s that the bacteria have developed resistant capabilities. That’s something that they’ve had for ages. Resistant genes are ancient. It’s the acquisition and expression of them that’s been changing – largely due to our activities, our widespread overuse of antibiotics.
SPENCER: First, I must expose my ignorance. You can straighten me out, and a lot of other confused people too. There are bacteria and there are viruses. There are antibiotics, there are vaccines, and there’s something called phages. Probably there are other magical stunts that can combat bacteria and/ or viruses. But some things are good for some purposes but not others. Help me get clear about all this.
KAHN: Let’s go to the basics here. What is the difference between a bacteria and a virus? A bacteria is a fully functioning living thing. It eats, it eliminates, it reproduces; it’s a single celled organism but it doesn’t drive a car, doesn’t own a house.
SPENCER: They also don’t have sex, right?
KAHN: Not true. They have little ‘pili’ where they can share genetic material. That’s a form of bacterial sex. They’re sharing genetic material. They share little circular bits of DNA called ‘plasmids.’ And often these plasmids have antimicrobial resistance genes that they very nicely share with each other. We’ll get to that later. So yes, bacteria can have sex, if that’s how you want to call it – the pili that they share with each other. So, bacteria, as I said, are complete living things.
Viruses, on the other hand, are technically not alive. They are purely strings of genetic material, whether it’s DNA or RNA, encased in a protein coat. They don’t eat, don’t eliminate. They’re parasites; they require infecting a cell, whether it’s a bacteria, one of our human cells, an animal cell or a plant cell. They require a living thing. to inject their genetic material and hijack the machinery to turn that cell into a virus-producing factory, of which the new viruses then burst out. So, it’s a very different mechanism.
SPENCER: And smaller than bacteria?
KAHN: Much smaller! They are infinitesimally small. You need an electron microscope to see them. They are strictly parasites – technically not alive, by our criteria.
SPENCER: They can hang around for thousands of years, right? I mean, people talk about things melting in the Arctic that could bring back to into existence viruses that existed 50,000 years ago. That wouldn’t be possible for bacteria, right? Bacteria die, right?
KAHN: Bacteria can stay in a dormant state. Some bacteria – anthrax for example – form spores.
SPENCER: That’s a new term you’ve thrown into the equation. Exactly what are spores?
KAHN: You know how some plants develop really hard seeds? Macadamia nuts, for example. You need a vise to crack those things. They can stay in the environment for prolonged periods of time. Think of a spore as like a macadamia nut. It’s very hard. It survives in the environment and it waits for the right conditions on order to convert to its metabolically active form.
SPENCER: So that’s where bacteria could be hiding?
KAHN: Yeah, if they form spores. And there’s evidence that viruses – bits of DNA – can travel inter-planetary! There’s been speculation that maybe life started somewhere else and came to this planet. But that’s another whole subject. It’s just a theory.
SPENCER: That’s another great topic to discuss sometime. But now we’ve got viruses and bacteria and viruses can be inside bacteria too.
KAHN: That’s right. The virus’s goal is to make more viruses. And in order for them to do that they have to inject their genetic material into a cell, whether that cell’s inside us or inside another animal or a plant or a bacteria. Different viruses have evolved to infect specific things.
SPENCER: So, there are no all-purpose viruses that would work as well on a plant as in my nose?
KAHN: I’m not sure. I don’t want to say never. There are fungi that can infect both plants and animals. I believe that there are some viruses that can as well.
SPENCER: Oh, I hadn’t thought about fungi. Fungi are not bacteria and not viruses, right? But like viruses, they are bad news.
KAHN: Well not always! We rely on fungi for bread. Yeast are fungi. We use it for baking, for beer production. We rely on many microbes. And in fact, there are plenty of good microbes in our gut microbiome that are as important for our health and well-being as our human cells.
We live in a microbial world. Our bodies are mostly microbial. The problem comes when microbes that are not beneficial for us get in. On the tree of life, we’re more closely related to fungi than to bacteria and other microbes. One of the reasons why anti-fungal medications are so toxic is because they are more closely genetically related to us than, say, bacteria.
SPENCER: Can viruses and bacteria infect fungi?
KAHN: Yes. Well, certainly viruses can infect fungi.
SPENCER: Has anyone ever tried to get a virus to infect a fungus in order to kill it because it’s something we don’t want?
KAHN: I’m not aware of experiments that are trying to kill fungi by using viruses. Now that’s an interesting question because we are using viruses to kill bacteria. Remember, I told you earlier that the bacteria have resistance genes, and some of them have developed resistance to virtually all of our antibiotics.
There is a specific class of viruses called bacteriophages that target specifically bacteria. They were used as a form of antibiotic back in the early 20th century. Now the challenge with them is that they are very specific. Each one only targets one specific bacteria and they’re not that easy to use. They are kind of nature’s antibacterial. Interest in them waned when antibiotics were discovered, which are easier and cheaper to use, less labor intensive. You have to isolate bacteriophages. You have to identify which ones specifically address the bacteria that you want to target. They’re labor intensive so interest in them waned.
With antibiotics, you can have what’s called the ‘shotgun approach.’ One antibiotic can target a whole bunch of bacteria. The challenge with that is that you’re killing off the good with the bad. So, you have a lot of problems when you give antibiotics. Ideally, you’re killing off mostly the bad but you’re also killing the good, so you can really mess up the microbiome that we need for health. So, as antimicrobial resistance gets worse, there’s a growing interest in developing these bacteriophages as either adjuncts or possibly substitutes for antibiotics.
SPENCER: Would they try to set up a system where they collect 1000 different bacteria that might be dangerous to somebody, and then, in advance, start growing phages that will react each bacterium – and keep them going and ready for somebody to come along and say “I need that one.”? I’ve heard that it takes weeks for them to get ready to use them on a person because they have to take a culture from the patient.
KAHN: It’s like personalized cancer care. You take the cancer cell and identify its weak genetic points and develop targeted therapies against that. Similarly, you have to identify the bacteria that’s causing the illness. But our diagnostics are not quite there yet – certainly not in the clinic setting. These bacteriophages are usually used with severe resistant infections and patients who are hospitalized – at least in the Western world.
But for the past hundred years, there was a clinic in Tbilisi, Georgia called the Eliava Institute.
SPENCER: I had a Montreal friend whose son had an infection in his leg that couldn’t be cured here. So, he went to Georgia – and it worked.
KAHN: That’s a famous center founded by George Eliava. It’s a sad, sordid history because he was apparently involved with the girlfriend of the head of Stalin’s secret police, and he wound up getting murdered. The Institute persisted despite his demise. They have a large library of bacteriophages. Somebody comes in and they identify the causative bacteria. They go to their library and find the best match and they create a cocktail of several different bacteriophages to use, either topically or to ingest or inject.
But you have to know what you’re treating, which is good and bad. It’s very targeted treatment, whereas in the West we typically do not identify the causative agent but just prescribe presumptively – for better or worse. When you treat presumptively with the ‘shotgun approach,’ hoping that whatever you prescribe is going to hit what’s causing the problem, sometimes you’ll make a mistake. The shotgun approach is worsening antimicrobial resistance because the bacteria develop resistance to these antibiotics.
SPENCER: Should they keep a library of these things? Do they have to keep reproducing them in order to replenish that library?
KAHN: The beautiful thing is that bacteriophages exist in the natural world. There are trillions of them all around us and in us. They’re abundant in sewage. The technologies to identify them really haven’t changed much over the hundred years. You take samples from the environment and see which phages are killing the bacteria. Those are the ones you want. So, you collect them and store them in your little vial.
SPENCER: Once you’ve got them in a vial, do you have to keep taking care of them? Or will those things stay there for 100 years, ready to be used?
KAHN: If you want to keep your phage in stock, you’re going to have to grow them by providing them with host cells which they can infect. So, it’s a maintenance problem. I don’t know the details, but it’s very labor intensive. Still, it is a strategy for dealing with resistant bacteria because, as the bacteria evolves, so do the phages. There’s kind of a tit for tat between them. It’s nature at its best. And I say that it’s best to work with nature rather than against nature. So, using bacteria phages are a clever strategy to work with nature against the bacteria that make the pathogens that make us sick.
So that’s one strategy for dealing with this whole anti-microbial resistance mess that we’re in. But it’s expensive, it’s labor-intensive and would require some technological advances to make it more accessible on a large scale
SPENCER: Suppose you have two different people getting sick – one in Thailand and one in Peru. How likely is it that they will be caused by exactly the same bacterium and could be killed by the same phage?
KAHN: Probably unlikely because you’re in completely different environments. It’s unlike an antibiotic where you can develop a pill and just distribute it. With phage treatment, you would have to have phage centers located in many different places where people could go and get personalized treatment.
SPENCER: How much would their bacteria vary according to their geography? Instead of comparing patients in Thailand and Peru, let’s say they were both from same town in Thailand. Is it more likely that if some if two people came down with a disease, it would be caused by the same bacteria because the bacteria are hosted in their environment>
KAHN: If, say, they got food poisoning, they probably ate the same food containing the same bacteria. Or if they got a skin infection from someplace in the soil, or a scratch from kitten. It’s really situational whether they got the same infection from the same microbe or not.
SPENCER: If you’re looking for cures, what else would you be doing to solve this crisis?
KAHN: I’ve always been a strong proponent of prevention. One challenge is about our wastes. There are eight billion humans on the planet. We have 30 billion terrestrial food animals. Collectively we produce at least 4 trillion kilograms of fecal waste every year. Our sanitation systems are only designed to process human waste, not animal waste, even though animals produce around 80% of this 4 trillion kilograms.
For the livestock, they’ve got huge indoor lagoons. We’ve got companion animals that are defecating. In some parts of the world they don’t have good sanitation systems for humans, much less for the animals. In a microbially dense environment we get food-borne and water-borne infections. We’ve got contaminated soils. These fecal microbes are contaminating the atmosphere with methane and nitrous oxide, which are greenhouse gases. So, we have to talk about prevention.
We need to learn how to live in our microbial world better and we’re doing a poor job of sanitation. Human and animal fecal waste contain many pathogens, including resistant bacteria. We need to figure out how to process it. We can use manure as a form of fertilizer. It has been replaced by large amounts of high-nitrogen, synthetic fertilizers that they use on agricultural soils. Agricultural soils contribute about 78% of the nitrous oxide into the atmosphere – that’s 165 times more potent as a greenhouse gas, trapping heat and carbon dioxide.
These wastes worsen antimicrobial resistance, contaminate our food and water, they make us sick, and they contaminate our atmosphere and worsen climate change. So we need to be talking about that crucial issue.
SPENCER: Let me ask something more about what antibiotics do. Do they just kill bacteria or do they also kill viruses?
KAHN: They don’t kill viruses but some antibiotics will kill bacteria. Other antibiotics will merely stun the bacteria to give your immune system the opportunity to clear them.
Antibiotics are useless against viruses. For that, you need an antiviral. Viruses are technically not alive so you cannot kill them. All you can do is either prevent them from attaching to the cell, mess up their reproductive machinery, or prevent them from breaking out of the cell. You can stop a virus from functioning, but you cannot kill it.SPENCER: That’s why we need vaccines?
KAHN: Vaccines are basically target practice for your immune system. When your immune system encounters a virus for the first time, it doesn’t know what to do with it. By the time it figures out, “Oh, this is not a good thing,” the viruses are widespread throughout your body and kill you. A vaccine gives you either the killed or the deactivated virus or a greatly weakened virus. Just something for your immune system to look at and say, “Oh, this is this is something new. What is it? This is something bad.” It gives the immune system time to practice attacking this new unknown thing. Once it’s developed those capabilities, your immune system is like your military, targeting invading viruses and bacteria with tiny missiles.
Some viruses, like HIV, which hide in our cells, are hard to develop a vaccine against. Malaria is a parasite, a whole organism that’s hard develop a vaccine against – although they appear to have developed one. Vaccines are a really great strategy for preventing or reducing the severity of illness. With antibiotics and antivirals, you only give them once you become infected, but vaccines are training your immune systems to fight against this invading organism.
After a few years, or maybe just six months, if it’s not practicing, it forgets. So, you need a booster. periodically to remind your immune system: “Hey, these things are out there. Don’t forget them.”
SPENCER: I used to work in a physician’s office, and we had something called DPT for babies. My impression was that it was lifelong. You give the baby this one little vaccine and he’s good for life.
KAHN: No, you need tetanus boosted every ten years. DPT is diphtheria, pertussis, and tetanus. Pertussis is whooping cough. It’s a bacterial infection and resurgent.
SPENCER: I understand that there have been outbreaks of measles lately. Why? Had parents not given their babies measles shots or had it lost the effect on them as adults?
KAHN: Are you familiar with the measles, vaccine and autism controversy? Andrew Wakefield published a paper stating that measles caused autism.
SPENCER: Oh yes. The thing that started all these anti-vaxxers.
KAHN: Yes, that caused significant damage in the public’s perception and trust of vaccines. The paper was ultimately identified as fraudulent and retracted but the damage was done. Many people now refuse to vaccinate their kids, so we’re seeing a resurgence of measles.
We require what’s called ‘herd immunity’ to break the chain of transmission. Measles is one of the most communicable viruses. One sick person can affect 18 or more people just by walking in the room. Very, very contagious. So, to break the chain of transmission, one way is social distancing, which is not fun. Another is to vaccinate children. But people are not vaccinating their kids, so that chain of transmission is going to continue.
SPENCER: I think people who refuse vaccination are really culpably antisocial.
KAHN: The US is an individualistic country, not thinking about others. That had a severe effect during COVID.
SPENCER: Let’s talk about the book you published several years ago.
KAHN: Okay. Part of The Politics of Anti-microbial Resistance is that the medical community was blaming the veterinary community as the cause of antimicrobial resistance. And the veterinary community was blaming the medical community – each service pointing fingers at the other. Okay, there’s a lot of overuse in both human and veterinary medicine. There are tons of overuse in both animal agriculture and plant agriculture. A lot of plants are getting sprayed with antibiotics.
SPENCER: But why would we care if they overuse it on plants? We don’t catch plant diseases.
KAHN: But if it’s bacteria that can protect us, and you’re spraying for it in the environment? Let me back up. Antimicrobial resistance is ancient and everywhere. These resistance genes have been found in the Arctic and the Antarctic, in places that have never seen human antibiotic use or exposure.
We long thought that bacteria had kind of a chemical warfare against each other for survival in the environment. But it appears to be much more subtle than that. These bacteria use minute amounts of these chemicals, not as warfare, but as a form of communication with each other. They communicate through chemicals – these little bits of DNA.
We’ve been blasting the environment with our antibiotic use. It’s in our urine and feces. The four trillion kilograms of fecal matter is going out into the environment, into the soil, affecting the microbiome of the planet in ways that we don’t fully understand.
But remember the bacterial sex we talked about earlier. They cooperatively share their resistance genes with each other through bacterial sex. They’re increasing the expression of these ancient genes to counteract the effect of our overuse.
Here’s an analogy. You and I communicate mainly through sound. I’m talking to you in a low, modulated voice. But what if a loud jet engine were here, blasting our ears? Resistance genes are kind of like noise-cancelling earphones. If I had a pair of noise cancelling earphones, I’d protect myself from the noise, and if I had an extra pair, I’d shared it with you. We’d protect each other from this assault. The bacteria are very nicely sharing with each other these resistance genes to protect each other. We’re making their lives unpleasant or deadly and they’re fighting back more effectively than we can produce new antibiotics. We’ll always be behind because there’s a lot more of them sharing these resistance genes than there are of us, trying to figure out antibiotics.
That’s why the strategy of bacteriophages is so important. We work with nature, not against it. I’m trying to learn to live more sustainably in our microbial world. To do that, we must clean up our waste.
SPENCER: Whatever we’ve already put out there as waste is still there. How long is that going to be causing troubles for these little friends of ours that we don’t want to kill? Can they return to normal?
KAHN: That’s a great question. How do we restore our natural world? I don’t even know if it’s possible. There are eight plus billion humans and three plus billion terrestrial food animals. Biodiversity has plummeted. We’ve altered the ecosystems. We have to figure out how to live more sustainably.
SPENCER: These antibiotics that we’re spraying around – do they live forever?
KAHN: Antibiotics are not alive. They’re chemicals. The question is, how long do these chemicals persist in the environment? I don’t have an answer.
SPENCER: What are you suggesting by way of cleaning up the environment?
KAHN: Some of these concentrated animal feedlots with thousands of animals produce as much manure as a midsize city. They’re in giant lagoons. If there’s a storm, lagoons burst and fecal matter spreads all over the place. It’s just not a good strategy.
SPENCER: But there’s a whole argument about holistic management of grazing. I tend to believe it. A guy named Allan Savory says that a lot of the world’s land is drying up because there are no longer herds of animals traveling around in packs. One beneficial thing that herds used to do was leave droppings and then trample the ground, stirring in the droppings. Savory says that we need to resume that to revive our soils. By that account, fecal droppings are a blessing.
KAHN: Our culture has decoupled animal agriculture from crop agriculture. We’ve got, as you said, the depletion of our soils even while the animals are producing massive amounts of fecal matter that are just being stored in these lagoons.
So yes, one strategy would be to reintegrate the animal with the crop to use the fertilizer. We’d have to make sure that they’re cleaned for our consumption because we don’t want to eat the animals’ fecal matter. But it would be more sustainable than relying on high-nitrogen synthetic fertilizer, which is currently being so detrimental.
SPENCER: I have a position on that. I’m promoting rock dust as a way of capturing CO2 from the atmosphere and sequestering it in soil. It’s a great alternative to synthetic fertilizers.
KAHN: There’s a number of strategies. There’s low-till, there’s drip agriculture, there are cover crops.
SPENCER: But if the food is grown in soil fertilized with manure from cows, we can’t keep it from our food.
KAHN: Ideally, we’ll wash off the manure to reduce the risk of food-borne illness. There are actually phage cocktails that you can spray on your food to eliminate the bacteria. That’s another viable agricultural use for phages.
SPENCER: Should we really have herds of animals again? I like the idea. I’m uncertain whether there can be agriculture that overall is carbon-negation, so that our meat production would not actually add more CO2, methane and stuff.
KAHN: That’s a fair challenge. The challenge with cows is that they are ruminants. Our cows have four chambers, one of which is a rumen – a fermentation chamber – and they’re burping out methane. Their methane burps are actually a large contributor to the methane greenhouse gas.
SPENCER: Our next forum on Monday will be about seaweed. One of the arguments is that now it is possible to reduce up to 90% of these enteric emissions by feeding the cows certain kinds of seaweed. But I still think that if we continue to have cows leaving their droppings, then stuff will get into our food.
KAHN: The question is: synthetic high nitrogen fertilizer versus cow droppings. The cow droppings would help replenish the soil but we would want to make sure that the droppings don’t infect pathogens and don’t infect us. So that’s one of the challenges. This is a microbial world and we just have to figure out how to live better in it. That’s the One Health approach.
Prevention is much better than treatment. But we need to work with nature, not against it hen we’re treating these infections, and we want to work with nature to reduce the contamination of our soils, our waters and our air that contribute to both greenhouse gases and to our illnesses and need for more antibiotics. All this is tied together. One Health recognizes the linkages between human, animal, plant, environmental, and eco-system health. This lets us see the big picture.
SPENCER: I consider my task as none of these things, because I’m not a scientist, but rather publicizing these discussions and trying to enlighten public opinion. Now, what campaign would you like to formulate to solve your problem? Should I try to get people to contact their MPs or what? What is your political campaign trying to do?
KAHN: The message should be positive. We need to live sustainably in our microbial world – with the microbes on the plants, on the animals, in the soils, the ecosystems, the world around us. And we need to clean up all these fecal wastes. We need to reintegrate animal and crop agriculture to replenish what has been depleted. In our agriculture, we can use bacteriophages for both agriculture and human health. That’s the message. People can pick what area they are most passionate about. We need to understand the ‘One Health’ concept and work together to live on our beautiful planet. Let’s clean it up.
SPENCER: What a wonderful message! Let’s talk again in the fall when your book is out. Bye! •
Laura Kahn is a leader in the One Health movement, now researching in Washington, D.C.
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