Steve: Welcome back to part 2 of this episode of the Scientific American podcast, Science Talk, posted on February 2nd, 2012. I'm Steve Mirsky. In the second part of my conversation with journalist and author Maryn McKenna, we talk about antibiotic resistance including MRSA, and we'll pull up the rear with a brief return to the subject of fecal transplants. Buckle up.
Steve: Let's talk about antibiotic resistance and agriculture, because that's such a huge issue. Much more antibiotics goes into agriculture than being administered to people who are sick.
McKenna: It's a really, really interesting and tangled story.
Steve: Most of it is with healthy animals.
McKenna: Right. So when we talk about beating back antibiotic resistance or at least slowing its emergence—which is something that I've been really interested in for a couple of years; I wrote a book about antibiotic resistance called Superbug—we tend to think of antibiotic misuse and overuse as something that people do, as something that doctors and patients do. Either people don't take their full antibiotic prescription; or they ask for antibiotics when they shouldn't because they have a viral illness like a cold; or physicians give antibiotics at the wrong time, maybe because they don't have enough time to spend in their office to explain to patients that what they have is a viral illness, not a cold; or maybe there's a psychosocial thing going on where people have to get to work and they don't have sick leave, and they have to put their kid in day care and their kid has a sniffle and the day care doesn't want to hear whether its bacterial or viral, they just want to know that the kid is on a prescription. Well, all of that is true. There's lots of evidence that in human medicine we misuse and overuse antibiotics. But it turns out that that's a fraction of what we do in agriculture. Eighty percent of the antibiotics that are sold in the United States every year go into farm animals, not into humans. And the vast, vast majority of those go into healthy animals. Now, it's important to say right upfront, no one that I know of disagrees with giving antibiotics to sick animals to make them well. That's just not, that's a nonstarter; no one is protesting that. But what's going on here instead, what most of those antibiotics are being used for, is to keep animals healthy in the extreme confinement conditions of very, very large scale farms. And there's prophylactic treatment in which they give it to healthy animals because the conditions in which they're held are likely to make them sick. And there's also something called growth promotion, which is basically giving, kind of, micro-doses of antibiotics to animals because it makes them put on weight, get up to market weight, faster. And if you're growing animals, essentially like widgets on a production line, it makes perfect sense to want to get them out of the farm as fast as possible and sell them and get in fresh ones. The problem with that is there are a number of byproducts of that practice that are, sort of, external to the experience of the farm, and one of the major byproducts is antibiotic resistance. The fascinating thing is this practice has been going on for a very, very long time and no one ever really noticed it outside of agriculture. It was actually the accidental creation of two pharmaceutical chemists back in the 1940s, who were looking for something to do with the byproducts of tetracycline manufacture. And for some reason that no one seems to have recorded, they decided to try giving the leftover carbohydrate mash in which they brewed the drugs to chickens, and the chickens got fat faster and from that an entire industry was born.
Steve: How do the antibiotic-resistant strains that are inevitably going to develop in an environment that's filled with antibiotics, how do those get out of whatever chicken coop or pig farm they're on and get out and affect the rest of us?
McKenna: Well, once and again, it all comes back to the gut. Because if you're giving antibiotics to animals especially so consistently, what happens is that they don't, their bodies don't use up all of those antibiotics, they don't fully process them. And so both the antibiotic residue and antibiotic-resistant bacteria pass out of the animals in their manure. Now some of them remain in the gut and when the animal is slaughtered, feces get everywhere. I mean, I don't think people really understand that about what goes on in a slaughterhouse, but it's very common for feces, as you extract, sort of, the inside of the animal to the outside of the animal, for feces to contaminate some part of the carcass; and then you've got antibiotic-resistant bacteria on the meat that the animals become, and that's how you end up with antibiotic-resistant bacteria on meat at the retail level.
Steve: And there's a lot of it.
McKenna: It's amazing, up to recent research, which we mentioned earlier, published in 2011, found drug-resistant staph on one out of four meat samples bought in a number of cities across the country.
Steve: And depending on the cut and whether its ground or whole, those numbers go way up.
McKenna: That's right. Yeah, and now it's much more likely, for instance, that if you have contamination on the outside of a solid piece of muscle, steak for instance or a whole turkey breast, you can do something to rinse it off to get that off. But if that whole muscle has been ground up into hamburger or ground turkey then what was on the outside is going to suddenly be on the inside, and unless you cook it really, really thoroughly, you may not be killing that bacteria. But, you know, even, it would be bad enough if antibiotic-resistant bacteria on meats of various kinds was the only problem, but it's not the only problem emerging from farms. Because the vast majority of those bacteria actually end up in manure lagoons, in places on very large farms, where manure is sort of stored until it can be disposed of by being sprayed on, either trucked away or sprayed on fields as fertilizer. So you've got antibiotic-resistant bacteria and antibiotic residues in these enormous ponds. Sometimes the surface of the ponds dries out and dust blows off; dust with antibiotic-resistant bacteria in it has been found downwind at very large farms. Sometimes it percolates down in the ground water. There's very good research showing antibiotic resistant-bacteria in surface waters, streams for instance, downstream of very large farms. Sometimes it goes home on the clothes and on the skins of the farm workers, which puts their families at particular risk. The thing is, these are all what an economist would consider externalities to the fundamental transaction of growing the animals, and so they're not something that agriculture itself has to account for because, the actual effects of those antibiotic resistant-bacteria of making someone ill, of interfering with someone's treatment, they happen very far away from that farm.
Steve: Right, so if you're just doing the economic workups, the cost, in terms of public health, doesn't get factored in.
McKenna: If you're only doing the economics of growing livestock in as efficient a manner as possible, antibiotic use makes a lot of sense, because it lets you get those animals out much faster. Now it's bad for the environment, it's bad for public health, it's bad for animal welfare, if you care about animal welfare, but none of those are actually central to the fundamental and economic transaction of growing the livestock itself.
Steve: So, factory farm is in many ways similar to two of the other really outstanding places, if you want to incubate a new strain of antibiotic resistant bacteria: a hospital or a prison; where you have a whole bunch of individuals living on top of each other and sharing microbes with each other at the same time as you are possibly, and definitely in the case of the factory farm, administering antibiotics to them.
McKenna: That's a really excellent analogy, and you're really correct. The first places that antibiotics resistance appeared as a problem that we noticed was in hospitals. I mean, for my sort of favorite bug, MRSA, which is what my book, Superbug, is about. The first MRSA strain appeared in 1961 in a hospital outside London, only 11 months after the drug to which it's resistant, methicillin—which is the M in MRSA—only 11 months after that came on the market. And MRSA appeared first in the United States in what was then called Boston City Hospital in 1968. So, hospitals first, then other places where people are confined and have bad hygiene and are close together and can't get away from something that's transporting the bacteria to them—that really describes prisons. And prisons were some of the earliest outbreaks of what we now think of as community-associated MRSA, but it also describes military barracks; and to a certain degree it also describes gyms and it also describes schools. And one of the places where community MRSA, for instance, has been a really serious problem has been among schools; and particularly among student athletes for something as simple as they're crowded together, they're sweaty and salty—staph in particular really likes salt for some reason—and they don't clean up after themselves. Kids don't shower after sports. So, there's been this really interesting and, sort of, kind of, under the radar increasing epidemic of antibiotic-resistant infections among kids in schools and particularly among kid athletes, such that the professional organizations for athletic trainers are really getting into the act to try to get kids to clean up after themselves again.
Steve: Have seen antibiotic-resistant staph outbreaks on National Football League teams as well?
McKenna: That's right, yeah. In the National Football League and also, really, in the NBA. In fact there are a number of football and basketball stars, both pros and in college, whose careers have been ended by this.
Steve: You reminded me as well: homeless shelters you could put on the list as well. It's theorized that in New York City in the '90s, there was a big outbreak of antibiotic-resistant TB that some people think was actually born in an armory that was being used as a shelter, right across the street from one of the major hospitals in the city.
McKenna: Right. And MDRTB—multidrug resistant TB—you know, we thought, TB is such an interesting story because we really thought we'd solved it. It was the HIV of the 19th century. It was extraordinarily potent, it moved really fast, it killed people who were very high profile, often lots of people in the creative class—the Brontës had it, a number of 19th century composers had it.
Steve: Stephen Crane, Chekhov.
McKenna: We thought that TB was solved, and then TB roared back again in the '90s subsequent to the HIV epidemic because HIV made people vulnerable to it. So TB is another example of how we, kind of, let antibiotic resistance get the better of us. When I was tracking MRSA outbreaks through the '80s and '90s in order to write my book, I noticed that, as I said, the first cases of hospital MRSA in the U.S. were in 1968. But it wasn't really until a major outbreak in a hospital in Seattle in 1980 that people really started taking it seriously. That was 12 years in which it promulgated across the country with no one ever really paying attention, until really, the curve was too far along to really dial it back.
Steve: Let's talk about MRSA for a second. In Superbug, you talk about the resistance, if you will, of the medical community to believe that there was such a thing as community MRSA rather than hospital MRSA. Could you talk about the difference there and why it was so difficult for them to accept that?
McKenna: That is such an interesting story. So, the first MRSA strain, 1961, shows up in three patients, actually two patients and a nurse, in a hospital outside London; crosses to the United States in 1968, starts with an outbreak in Boston, what used to be called Boston City Hospital and is now the Boston University Medical Center. Seventeen men and a healthcare worker; the outbreak was started by an elderly man, who was admitted from a nursing home with what looks like bronchitis, turns out to be MRSA pneumonia. And it just kind of trickles across the country and no one's really paying attention until this big outbreak in 1980 in Harborview Medical Center in Seattle. Just a really dramatic outbreak that started accidentally by a burn patient who's been treated in a hospital in Houston and gets transferred to the Pacific Northwest because his family is there; brings MRSA with him from the hospital in Houston and the strain bounces from burn patient to burn patient to the ICU to the rehab unit, it goes on for more than 15 months, it kills a number of people. They actually tear down both the burn unit and the ICU and build new ones and the outbreak keeps going. So that's the outbreak that eventually convinces American medicine that MRSA is a hospital organism to be feared. The problem is we got that message so thoroughly that it never really occurred to anyone that MRSA would keep evolving. So, fast forward 15 more years from the Harborview outbreak to the University of Chicago Children's Hospital on the Southside of Chicago, a beautiful enormous hospital in the midst of very poor neighborhoods. And two of the pediatric infectious disease specialists in that hospital are just passing each other in the hallway and they have a hall way conversation, the way academic physicians do everyday; and one of them says to the other that they're seeing something odd, they're seeing kids with MRSA infections, this hospital organism that everyone goes in fear of now, but the kids are in the ER. Now if you think about that for a minute, that doesn't, from their understanding of MRSA at that time, that made no sense. Because an ER is a door that only swings one way, and that's into the hospital. It never happens that you're in the hospital and then go down to the ER. So, what this meant was that there were kids with what everyone understood to be a hospital infection, but they hadn't yet been in the hospital. So, these two physicians did a study; they looked at what they had, they looked at charts from five years earlier, they drilled back into their hospital freezers and found blood samples from patients from currently and patients from five years earlier as a comparison, and discovered that in five years the occurrence of MRSA in kids who had not been in the hospital yet had gone up 25-fold. So, this looked like something that American medicine needed to be alerted to and so they wrote up this study, and they sent it to a major medical journal and the major medical journal basically said that they had made a mistake, they did not know what they were doing. Everyone understood that MRSA was only a hospital organism, and why were they wasting their time. So, they took their paper back and they worked on it for another 18 months and they eventually sent back some more, some genetic fingerprinting proof that this was actually MRSA, and the journal somewhat reluctantly accepted the paper. So, from that paper, that was in 1998 that it was eventually published, we are now in the midst of a community MRSA epidemic of about seven million cases a year; seven million cases that go to a primary care or to an ER for treatment every year for skin and soft tissue infection. The actual size of the epidemic is probably larger than that.
Steve: How are people out in the community getting it?
McKenna: Well, MRSA is a really fascinating tricky organism. So just unpack that acronym for a minute. MRSA, M-R-S-A, means "methicillin-resistant Staphylococcus aureus". Methicillin, that first word, is the name of the drug that was invented in 1960 to deal with staph that had become resistant to penicillin, the first antibiotic. Staphylococcus aureus, what most people call staph, is an incredibly common bug in our lives and in our environments. It has evolved the unique trick of living in harmony with us. It's what's called a commensal organism; it lives on our skin and inside our nostrils and in some other warm salty places on our bodies, warm damp places, and most of the time it doesn't makes us sick. But if it gets from the outside of the body to the inside of the body, then it can really be formidable. And in the pre-antibiotic era, just plain ordinary staph infections, if you got a staph infection of the blood or staph infection of the valves of the heart, there's a better than one in two chance that you're going to die from it. Now antibiotics were supposed to fix that, but now that staph has become resistant to not just the original methicillin but dozens of antibiotics that are used in medicine everyday, we're creeping back to that pre-antibiotic era of staph, resistant staph now, being really deadly. But staph still, even though it acquired this resistance, it still lives on our skins and in our nostrils and often doesn't make us sick; probably a third of the population walks around with regular drug-sensitive staph on them at any time and at least 2 percent, maybe more now, of the population has MRSA on them at some time. Exactly who picks it up and how long that state of colonization, as it's called, persists and why it persists and who gets sick is still somewhat mysterious despite the fact that staph is such a well-studied bug. But one of the interesting things that's happened is that as staph picks up new genetic material, including the genetic material that confers resistance, it also developed the ability to not just exploit wounds and tears in the skin, which is how staph always used to make us sick; but it's managed now to start breaking through intact skin. So you could have it just on your skin and have it not be making you sick and suddenly you'll develop something that most people describe as a spider bite. In fact these days in a large part of the country, if you go into an emergency room and say, "I have this red hot thing that really hurts; I think it's a spider bite", most emergency room physicians will not treat you for spider bite, they'll test you to see if you have MRSA instead.
Steve: What are the hopes, your book talks near the end about the hopes for a vaccine against MRSA. That seems like a really hard nut to crack.
McKenna: It's really interesting that you ask that. I've actually been taking a look at some of the staph-vaccine efforts recently. So people always thought that it wouldn't really be worthwhile to make a vaccine against MRSA, because the people to whom you would give it would just be people like, for instance, people who are going in for a heart surgery and maybe they would be at risk of a surgical infection. Now that there is this new recognition dating back to the understanding that MRSA is a community organism and now causes millions of cases every year out in the community, pharmaceutical companies are starting to take a second look at whether it would be worthwhile to make a staph vaccine and try to give it to everyone. So, if you think of it in that way, suddenly there's a very large market there. It turns out though that the immunology of making a staph vaccine is really complicated. As far as we know, if you get a staph infection, that does not protect you against getting another staph infection. In fact it's pretty well known that MRSA infections in some people are unfortunately really recurrent and you can get them five, six, seven times. So, if you don't develop a natural immunity when you have the infection, then how do you create artificial immunity in a vaccine? No one has answered that question yet. In fact, there have been several trials that have gone all the way to phase III, to human trials, and they looked good and then in phase III they failed. But I've been just recently looking around, and though they haven't made a big deal out of it, it looks like almost every major pharma company is now working on a staph vaccine. So, not only do they think there's a market there, but they must think that there's some immunological magic that can be worked that will actually make this possible. I think probably in the next couple of years, we'll see.
Steve: What's the scariest thing that's out there right now?
McKenna: So, when I was writing my book Superbug, and taking a look at increasing amounts of resistance in staph—and make no mistake, some strains of staph are now effectively untreatable; there's only one or two drugs left and the drugs that treat it are drugs that date back to the 1950s, to the glory days of antibiotic drug development, there are very few new drugs for staph. Physicians would say to me, "Oh, you think MRSA is scary. I've got something for you that is scarier." And what they would start to tell me about is something called highly-resistant gram-negative bacteria. Now that requires a little explanation. One of the ways that you, sort of, classify bacteria is by their response to a particular stain that makes it visible under a microscope that was invented by a Danish chemist named Hans Gram in the 19th century. Bacteria are either gram-positive or gram-negative. MRSA as it happens, staph, is a gram-positive. But what that designation, gram-positive versus gram-negative, what it's actually indicating is how complex the wall of the membrane of the bacterium is. Gram-negatives have a double layered cell membrane and the reason that's important is…
Steve: It won't take the stain.
McKenna: Right, they don't take the stain, that's why they look different than a gram-positive. The reason why that double-walled situation is important is not really because they take the stain differently, it's because most antibiotics work on the bacteria by doing something with the cell wall. They either explode the cell wall or they get through the cell wall to mess with the inside of the bacterium or they keep the bacterium from making new cell wall as it's dividing. So, if you have a cell wall that's more complex, then it's harder to design drugs to get through it, to do something to the bacterium. As a result, there are fewer drugs to treat gram-negatives and gram-negatives have suddenly become much more resistant. Last year, people were talking a lot about a resistance factor called NDM1, which actually stands for New Delhi metallo-beta-lactamase 1. It's a gene and enzyme that's showing up in a lot of gram-negative bacteria. It is effectively untreatable. There is only one old drug that works for it. There's another form of resistance in gram-negatives. This one tends to be known as CRKP—that stands for carbapenem-resistant Klebsiella pneumoniae. Klebsiella pneumoniae is one of the most common gram-negatives, major hospital infection; carbapenems are one of the drug classes of last resort. That, NDM1, appears to have come first from India, but carbapenem resistance is home grown, it actually started in the United States and then spread across the world. All of these gram-negatives, these difficult–to-treat bacteria are now becoming highly, highly resistant. And it turns out that the resistance is very promiscuous, it spreads very easily to other gram-negative bacteria. So, one of the most common gram-negative bacteria in our lives is E. coli, which we all carry; it's in the gut of every warm-blooded thing, including in us. And E. coli is now picking up this extreme-resistance DNA. That means that this extreme resistance could be very widely distributed in our environment before we know it, and then we really could be in trouble.
Steve: Because E. coli outbreaks are relatively common.
McKenna: E. coli outbreaks are common, but E. coli, if you touch that door handle over there, there's probably E. coli on it, even though we're all supposed to wash our hands after we go to the bathroom, there's E. coli in our environment everywhere. Because E. coli is in, you know, the feces of every warm-blooded thing, it's on practically every surface that you could think of, no matter how clean we think we are. And that's one thing, if E. coli is something that would be easily treatable if it happened to make you sick. But if it's something that's highly resistant, and it's highly distributed in our environment in a way that we're not keeping track of, that could really be an unpleasant situation.
Steve: So, that's the thing that you're hearing from physicians that they're really afraid of?
McKenna: Right. Highly resistant gram-negatives is our next big challenge.
Steve: Which brings us back to where we started because you want to make sure when you do those microbiome transplants that the E. coli is good, healthy E. coli and you can kill it if you have to.
McKenna: So, we should say that if people are the donors in fecal transplants or microbiome transplants, so we've agreed to call them today, they do get checked; they get checked to see if they have any gut diseases and they also get checked in the same way that a blood donor gets checked, to see if they have basically any communicable diseases. Because you don't want to be passing along a disease instead of a cure. And so there actually is one institution that is now starting to use sort of universal donors. You don't recruit your donor yourself from your family or someone that you're close to, someone that you live with. In fact they screen their healthcare workers and then their healthcare workers serve as donors. They process the transplant material and then they freeze it, and that way they can just defrost it and pop it in when they need to.
Steve: Right, the choice of using a family member was really an aesthetic choice. If you can have somebody's poop, you'd prefer to have somebody. (laughs)
McKenna: Somebody that you're already intimate with in some manner. And lots of people use a wife or a husband, boyfriend, girlfriend, mother, father. Although I have had some people say to me, some people who're not involved in the story that I wrote, that they actually question whether that's such a smart choice. The reason is because if you have some sort of illness like Clostridium difficile, for instance, it's possible that somebody else in your household is already colonized with that as well, so you might not actually be making yourself quite, it might not be as safe as we think. It might actually be safer to use universal donors. That is one of the things that has to be worked out, if we actually get to the point where we can study this.
Steve: It's fascinating stuff. So you're going to be in Scientific American basically every other month.
McKenna: That's right.
Steve: Hey, this was great talking to you.
McKenna: My pleasure to be here. Thank you.
Steve: We'll be hearing from Maryn McKenna on regular basis to talk about her ongoing contributions to Scientific American magazine. In the meantime, get your science news at www.ScientificAmerican.com, where you can also check out the section on citizen science. These are crowd-sourced research projects such as bird counting, meteor spotting or whale call listening, where your efforts can speed the pace of discovery. And follow us on Twitter, where you'll get a tweet every time a new item hits our Web site. Our Twitter name is @sciam. S-C-I-A-M. For Scientific American's Science Talk, I'm Steve Mirsky. Thanks for clicking on us.
Web sites related to this episode include www.marynmckenna.com and Swapping Germs: Should Fecal Transplants Become Routine for Debilitating Diarrhea?