Making Sense with Sam Harris - #166 — The Plague Years

Episode Date: August 21, 2019

Sam Harris speaks with Matt McCarthy about his book "Superbugs: The Race to Stop an Epidemic." They discuss the problem of drug resistant bacteria, fungi, parasites, and viruses, and the failure of the pharmaceutical industry to keep pace with evolution. If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.

Thank you. of the Making Sense Podcast, you'll need to subscribe at SamHarris.org. There you'll find our private RSS feed to add to your favorite podcatcher, along with other subscriber-only content. We don't run ads on the podcast, and therefore it's made possible entirely through the support of our subscribers. So if you enjoy what we're doing here, please consider becoming one. Welcome to the Making Sense Podcast. This is Sam Harris. No housekeeping today. I'm going to jump right into it.

Today I'm speaking with Matt McCarthy. Matt is an infectious disease doctor and a professor of medicine at Cornell, where he also serves on the ethics committee. His writing has appeared in the New England Journal of Medicine, Sports Illustrated, Slate, and other journals. He's the author of several books, and his latest is Superbugs, The Race to Stop an Epidemic. And that's what we talk about today. The problem that many of the drugs we use to treat infectious disease are now failing, and will always be failing. We're in a perpetual arms race against evolution and the emergence of new bugs that our immune systems have never seen. And this, quite amazingly, is a problem that is receiving very little attention, and yet it's on the short list of things that could utterly transform the

character of human life, very much for the worse. It's also on the short list of problems for which the market appears to offer no solution, as we will discuss. So now, without further delay, I bring you Matt McCarthy. I am here with Matt McCarthy. Matt, thanks for coming on the podcast. Oh, thanks for having me. So you have written a book that could be terrifying. You try to be as hopeful as you can be throughout, but God, this topic is just, it's brutal. I mean, this could be my own germ phobia creeping in here, but you have written a book, Superbugs, The Race to Stop an Epidemic. And this is a topic I've been worrying about for a long time. And I think ever since the first Ebola scare

and some of the books that followed, I mean, now we're talking, well, it must have been 1999 or thereabouts, maybe earlier when, I remember Laurie Garrett wrote a big book about the prospect of emerging pandemics. Before we jump into the topic, tell us how you got into infectious disease and just what your focus has been. Yeah, well, I'm glad that you've been worrying about this for a while because not enough people have been thinking about superbugs. And I think the first thing is it's useful to define the term. Some people say that drug-resistant bacteria are superbugs, but I take a much broader look at it and say that what we're really talking about are drug-resistant fungi and parasites and viruses and all kinds of living things that can come and attack us. And writing this book, I wasn't trying to freak people out, but I think

that has been sort of the fallout is that people read this and go, oh man, this is a big deal. And those of us in infectious diseases have been trying to sound the alarm about this for a while. You know, the World Health Organization just came out and said that superbugs are going to be a bigger killer than heart disease and cancer by 2050. And so, you know, how I got into this, it wasn't something that I'd always dreamed of being an infectious disease specialist. I was a first-year medical student at Harvard in 2003, and I heard a lecture by a young and charismatic infectious disease doctor named Paul Farmer. And he has traveled to Haiti and all over the world bringing drugs to people who couldn't afford them, bringing antibiotics and

HIV medicines and tuberculosis medicines to people. And I just fell under his sway. And I said, this is the guy. I want to do what he does. And six months later, I found myself in Western Africa hunting for the Ebola virus and trying to become an infectious disease doctor. And so that was, you know, 15 years ago. And so that, you know, sort of launched me in this career of trying to find what's going to be the next big pandemic, what's going to be the thing that gets to us, and how do we attack that, and how do we come up with treatments to stave off the next big thing? Yeah, I mean, one problem is that many of us have forgotten, or we never knew, in fact, how scary it was to live in a world where

infectious diseases were ascendant. We have forgotten what it's like for people to routinely die from tetanus and other wound infections. The whole generations of people were moving to warmer climates, however ineffectually, to try to mitigate their tuberculosis, which would kill them anyway. And we lived in a world for the longest time, forever, where there was just simply no guarantee or even promise that infections could be reliably treated. And then we had this fundamental breakthrough, which you detail in your book. I mean, penicillin was the first, you know, widely available antibiotic, and it really ushered in a golden age when

you could cure, you could expect to cure, you know, all of these invisible agents of death, and we seem to have taken it for granted up to the point where now we have fallen out of that happy condition. Well, you nailed it. I mean, this is the thing that most people don't realize is the luxury we have of antibiotics. As you said, penicillin ushered in the golden era of the 1950s where every month or two we were pumping out a new life-saving drug. And the life expectancy ballooned because of all of these new drugs. And then what happened was a number of prominent scientists, Nobel laureates, came out and said, you know, we got this infectious disease thing kicked. It's time to move on to more

pressing matters like heart disease and cancer. And the pharmaceutical industry responded and started making chemotherapy drugs and blood thinners and all of these lucrative things just as the superbugs were starting to mutate and to evolve and to become resistant to our treatments. And so now we're finding that as we're finally paying attention to this issue, we're behind the eight ball in a sense because we're playing catch up. The drugs aren't working as well as they used to and we're scrambling eight ball in a sense, because we're playing catch up. The drugs aren't working as well as they used to. And we're scrambling to find the next generation of life-saving drugs. And, you know, I'm reminded of this every single day when I walk into the hospital,

the first place I go is the emergency room. And I meet the patients who have these drug-resistant infections. And that's actually what led me to write this book is that, you know, people have talked about superbugs before. They've talked about the policy, about the science behind it, all of the stuff sort of at a 30,000-foot view. But what I was interested in were the patient stories and the lives that are completely derailed by these things. And the fact that the pharmaceutical industry is losing interest in making new antibiotics is devastating for tens of thousands of people. And so, you know, I'm trying to raise awareness, but also say, here's how we got in this mess, and here's how we get out of it.

So let's talk about, we'll talk about the ways in which the business model of the pharmaceutical industry is not helping us here, and the market is not helping us here. But before we get there, let's just talk about the basic science. What we have is, it really could have been foreseen based on evolutionary principles. I mean, this isn't surprising that we have bugs that can mutate and become resistant to the treatments we devise for them. And again, the reminders of this happening are everywhere. We're recording this on a Monday. Yesterday, the front page of the Sunday New York Times had a story on urinary tract infections

showing antibiotic resistance to a surprising degree, something like 30% are resistant to most antibiotics at this point. It really is a pressing concern, but it's not just a matter of bugs evolving and getting around our antibiotics, it's also just the fact that there are so-called super bugs everywhere as yet unencountered by us because there are bacteria in the soil and elsewhere, which our immune system hasn't devised any response to and our drugs can't anticipate. And so whether they mutate or not, we are very likely to encounter so-called superbugs in the future. You're absolutely right. And one of the big problems we have is how doctors and scientists

talk about these superbugs. You mentioned that front page Science Times article. I know the guy who wrote that piece because he's interviewed me before. And one of the quotes from that article is that this level of antibiotic resistance is shocking. And I read that and I thought, shocking to who? Because doctors know this and scientists know this. But if this is shocking to the lay public, that's because we haven't done a good enough job of explaining exactly how this is happening. But, you know, we just had a new rollover with first-year doctors who start in July, and every one of them knows by the third day of work that the antibiotics that they used in medical school are no longer working, and they

got to use a new crop of drugs just to treat people. And that's because the bacteria are evolving, as you mentioned, and they're coming up with these ingenious ways to destroy the antibiotics that we've relied upon for a generation. One of the things they do is they make these things called efflux pumps, which are like microscopic vacuum cleaners. And they suck up antibiotics and they spit them out. And then they use these enzymes that can chop up antibiotics. And so, what we do and what my research is, is we look for new ways to fool the bacteria. And so, one thing we found, for example, is that bacteria love iron. So, we'll use a Trojan horse

approach where we will attach an antibiotic to iron with the hope that the bacteria will see that iron and eat it and suck it up. And along with it, the antibiotic will go inside the cell and kill it. And we found that to be a pretty successful method so far for killing certain types of superbugs. And so, you know, the stuff that I do is, as I mentioned before, kind of scary stuff. But I'm also really excited and optimistic about all of the amazing science that's going on where we're constantly trying to fool the bacteria and come up with the way to save, you know, millions of lives. It's extraordinary, the kind of science that's being done. And I don't

think we're talking about it enough. You know, much of the work that you see in the newspapers has to do with the outbreaks or with the evolution of these drug-resistant bacteria. But I'd like to see a bit more about the profiles of the scientists who are coming up with new cures. Yeah, I mean, I can see the basis for hope, although we might be a little slow in getting there. But, you know, it's the difference between not having a remedy and having one that actually works and works as emphatically as an antibiotic that works, does in fact work, is just amazing. The 1950s must have been a mind-blowing decade to live through, to suddenly see these appalling diseases cured. I mean, now we're talking about not just antibiotics, but let's add vaccines to that picture. And then it just begins to look like every previous generation of humanity begins to look just unfortunate for having been born at the wrong time, because now

we have these cures for diseases that people can just forget about for the rest of their lives. And yet the problem, as you point out in your book, is that we should have always known that the arms race would never stop. These microorganisms are evolving quickly. And of course, our treatment, and in the worst case, our misuse of antibiotics is creating a selection pressure which will select for resistance. Absolutely, yeah. And I opened my book with a scene from the pre-antibiotic era, which is that we're on a battlefield in France, and there are these soldiers who are getting hit with shrapnel, and they're getting infections. And what do you do

before there are antibiotics? Well, you can try antiseptic fluid. It didn't work all that well. Or you can try a hacksaw. And that increasingly is what people have to do, is just go to the hacksaw and cut somebody's leg off to prevent them from getting an infection. And the reason for that is that if the infection that's on the skin or on the leg gets into the blood, that's called sepsis. And if you have sepsis, you're going to die without antibiotics. And so, you know, I wanted to paint that picture for people to recognize that we're heading to a pre-antibiotic era where the drugs we've relied upon for 75 years don't work anymore. And this is, you know, it's not a period to say, it's not a doomsday scenario.

We have a chance to invest in new treatments, but we have to do so selectively and carefully. And this is really an inflection point for humanity where we can say, this is an important issue. It's like global warming. It's like whatever else, you whatever else you hear about every day. This needs to be talked about in the same breath as a danger that we can invest in and come up with cures for. Let's talk about the problem of overuse, which is part of what got us here. I mean, I guess we would have gotten here even if we'd used these drugs as circumspectly as possible. even if we'd use these drugs as circumspectly as possible.

But there is this pervasive problem of overuse, and I'm wondering if the incentives are misaligned here between the individual and society, or if there's just a new way of understanding this. Because when I think about what most people's experience is in getting sick or watching their kid get sick and then facing the question of whether to treat with an antibiotic, it has been a very frequent experience for many of us to be prescribed an antibiotic essentially to be on the safe side.

Just it's prescribed empirically. You haven't even gotten to the point where an infection has been cultured and you know precisely what it's responsive to. You're given a broad spectrum antibiotic and this is just the prudent thing to do. And now we're stepping back and saying, well, this is not great for society because, well, this is not great for society because, again, we're part of the arms race that is creating a selection environment for superbugs. But it's part of the problem here that what is, in fact, prudent for an individual is raising the risk for society? Or are the risks actually the same? I mean, that is, when you're taking an antibiotic, as it's said, just to be on the safe side, are you actually running the risk of breeding a superbug that is likely to be a problem for you first? Or is it conceivable that

you're actually being prudent for yourself, but conceivably becoming a problem for society and how you're using these drugs? Well, I'm a medical school professor at Cornell, and that question that you just asked is what comes up on rounds almost every single day in various iterations, which is, we've got a patient in front of us who may have an infection and we're not sure, do we give them an antibiotic just to be on the safe side? And generations of young doctors and old doctors have been dealing with that question. I'll tell you, I was given a talk about superbugs a couple of weeks ago, and there was a guy who raised his hand and said, you know how locusts were cast upon the earth as a judgment for human behavior?

Do you think superbugs have been cast upon the earth as a similar judgment for human behavior? And the question caught me off guard at first, but there's an argument to be made that in the same way that we brought this on ourselves, and the issue really is on the small scale and the large scale. On the small scale, we've got doctors who are prescribing antibiotics, as you mentioned, just to be on the safe side. And that's no longer good enough as an excuse to prescribe something. And we've created a mechanism to check that. We have these people in the hospital who are called antibiotic stewards. And if you want to prescribe an antibiotic, one of our powerful drugs,

the steward has to approve it. And that's a job that I've had before. And I'll tell you, it's a thankless job because what happens is a surgeon orders an expensive antibiotic, and then I have to call them and say, I'm sorry, that's the wrong drug. And they say, oh, come on, please. I've been doing this 20 years. This is the drug I use. And I have to say, well, not anymore. There's a better option for you. And so, we're trying to check that the doctor's misprescribing things. But also, this is about patients can do a better job as well. You know, if your doctor prescribes five days of an antibiotic and you stop taking it after day two because you're feeling better, that gives the bugs a

chance to mutate and to evolve because you're not killing all of them. And so it selects out the ones that can survive. And so that's sort of on the small scale how we can be doing a better job. But let me just ask you about the logic of that, Matt. When the steward is saying, no, no, don't use that drug, use this one. Is that a case where he or she is trying to preserve the efficacy of the last line defenses we have? Absolutely. And so what happens is, I'll give you an example. There's an antibiotic called meropenem that we love using because it is so strong and it wipes out just about everything. And so if you're a doctor who just performed a complicated abdominal surgery, you want things to go well for that patient, you're going to ask for

meropenem. And I'm going to say, well, based on everything we know about the patient and the environment and the type of surgery you did, you could use ceftriaxone, which is not nearly as strong. And then we have to have an argument about how to go forward. And you know, I was listening to your podcast with Ricky Gervais, and he started out by telling you that there's no place for nuanced arguments anymore. And I felt so bad for him because all I do is have nuanced arguments with people all day long. And I have many nuanced arguments about antibiotics with very sharp surgeons and clinicians who really are advocating for their patient. And we have to be the ones as stewards to say that's, narrowly construed and the interests of society with respect to a choice about which drug to use. Absolutely. And, you know, this is, I'm on the

ethics committee and my research interests sort of are the intersection of infectious diseases and medical ethics. And what we talk about a lot and what I study is, what do you do if you're a doctor and you have a patient who's got, let's say, two weeks to live, they've got terminal cancer, and they get a superbug infection? Do you treat them with one of the powerful antibiotics that we have, one of our precious drugs in the arsenal, and potentially breed resistance and potentially breed superbugs, but to save that patient who's only got a few weeks to live. As I've found, doctors approach that question very differently. And there's no uniform answer for them. And so

sort of the next generation of clinicians are sort of winging it and figuring it out on the fly, which is how do you make life and death decisions when there is no formal training in how to do that? And so that's sort of on the small scale question of antibiotics. And then there's the larger scale issue, which is that we are using syphilis drugs and tuberculosis drugs in our orange groves. We're using our powerful fungal drugs in tulip gardens. We're pumping meat producing animals full of antibiotics. And, you know, whenever people

hear this, they say, well, that's terrible. That should stop. But the reason that it doesn't stop is that there are powerful lobbies behind Big Orange, you know, the meat industry. Big Tulip is something that you have to contend with. And these are things that allow, these groups allow the antibiotics to go in places they shouldn't. And then when we search the soil around those tulips, it's full of superbugs. And if you're somebody with a weakened immune system, you breathe in the wrong thing, you could end up in the intensive care unit. And we're trying to become much more judicious about how we use those drugs. So how are oranges and our tulips getting syphilis? Are they going to brothels? prescribing practices all over the world. And that brings up another issue, which is the more we look

for superbugs, the more we find them. And people try to categorize what's the burden of disease or what's the burden of these things around the world. We don't even know what's going on in Africa or in many places in sub-Saharan Africa, in Bangladesh, in India. Every time we start looking for superbugs, we end up finding much more than we expected. And I think that that's only going to continue to grow in the years ahead. And so, you know, part of it is getting better diagnostics so that we can know what we're dealing with so that we can come up with treatment plans. As far as the source of each new antibiotic, what percentage of them come from nature? I mean, penicillin,

it was a compound produced by a fungus, right? So how much of our drug development is a matter of finding happy accidents in nature and how much is us synthesizing new drugs based on a first principle understanding of the target microbe. Yeah, you hit on the two major approaches, which is, do we just get lucky and hope for the best, or do we build a new antibiotic? And both approaches have worked. What we're finding is that it's getting to be prohibitively expensive to build new antibiotics, atom by atom or molecule by molecule. So what people are doing now is they're searching in the soil. And the reason for that is that beneath our feet, there's this subterranean

warfare where survival of the fittest, bacteria and fungi are pumping out chemicals to kill each other. And if we can pull one of those out, you've got yourself an antibiotic. The problem is that it typically costs about a billion dollars and 10 years of testing to show that that chemical is safe and effective as an antibiotic. And fewer and fewer companies want to take that financial risk because if they get that drug approved, you know, compare it to a blood pressure medicine or a lipid lowering agent, these drugs, antibiotics are prescribed. The doctors are very stingy about prescribing them. They're only prescribed in short courses. And then even that great new antibiotic is going to wear out its welcome. So these companies are saying, no, thank you. We don't even want to go on the fishing expedition anymore. And so that has kind

of led us to what I consider the most important medical issue that no one is talking about, which is that the antibiotic market is broken. And we should be asking every politician, every political candidate, what are you going to do to fix it? If you'd like to continue listening to this conversation, you'll need to subscribe at fix it. The Making Sense podcast is ad-free and relies entirely on listener support. And you can subscribe now at SamHarris.org.