Ramanan Laxminarayan: The Global Reach of Resistance

Laxminarayan is vice president for research and policy at the Public Health Foundation of India, which works with the government to create a national policy on antibiotic resistance. He’s also executive director of the Center for Disease Dynamics and Economic Policy, which works around the world on the issue. This is the edited transcript of an interview with FRONTLINE conducted on July 26, 2013.

So you’ve identified this problem of drug resistance. What is it? How does it work? Why should we care?

We haven’t had antibiotics, these miracles drugs, for very long. We’ve only had antibiotics in use in modern medicine since probably the early 1940s.

They make a lot of things possible. Because of these drugs, we don’t die of infection diseases. We’re able to have transplants. We’re able to have surgeries, which require the human body to be kept open for long periods of time without the risk of infection. So these drugs are really the basis on which modern medicine rests.

Over time, as we’ve used more of these antibiotics, they have managed to kill off the bacteria that tend to be susceptible to the antibiotics and can be killed off by them. And the bacteria that remain are resistant. And over time, the entire population of bacteria in the environment, in our bodies, are composed of these resistant bacteria that just don’t respond to the antibiotics.

Now we’re in a situation where many of the drugs that used to work for us before no longer work, which means that patients have to be in hospitals for longer. They’re more likely to die, and in poor countries like India and Sub-Saharan Africa, many people cannot afford these second-line drugs to begin with.

vSo have we sort of done this to ourselves? Is this a problem of mismanagement of antibiotics?

To be fair, we’ve used antibiotics both appropriately and inappropriately over time. Appropriately used, they can cure disease, and they have saved millions of lives. Used inappropriately, they don’t benefit people, but they do create drug resistance.

Certainly there have been many instances where we have used them inappropriately, both in human medicine as well as in agriculture, where particularly in the United States and previously in Europe large of quantities of antibiotics were used as growth promoters, essentially to make farm animals grow faster and bring them to market faster. There are many ways in which we have abused antibiotics, and certainly we’re paying the price.

So what you’re saying is that the bugs are fighting back? …

Interestingly, we tend to categorize this as a battle between us and the bugs. It’s not so much a battle as just Darwinian selection.

So the bugs are sitting there. They’re multiplying. By the time we’ve had this conversation, the bugs have had children and grandchildren, so to speak. As they reproduce, the ones that are capable of reproducing are the ones that have not been killed off by antibiotics.

As we consistently select in favor of the ones that are resistant, we’re really stacking the odds against ourselves and in favor of these resistant bacteria. This is almost like running on a treadmill, but to stay in the same place, we have to run faster and faster.

There’s been a lot of talk about the new dangers of these Gram-negative bacteria and resistance. Can you explain that to me? Why is that different than what we experienced before? What’s happening?

So there are two broad categories of bacteria: the Gram positives, which the Gram stands for a Gram stain, so if they’re stained by this Gram stain — with a capital “G” — then they call it Gram positives; if they’re not stained, then they are Gram negatives.

The Gram negatives tend to be more difficult to treat in general, and also there are fewer drugs available to treat these Gram-negative bacteria. It’s also the case that Gram-negative bacteria are much more common in poorer countries and tropical countries, and there is a temperature gradient where Gram-positive bacteria are more common in the United States and in Europe.

There has been a large amount of antibiotic use against the Gram-negative bacteria, and over time, the number of drugs that we have in the pipeline, in the arsenal, to treat Gram-negative bacteria has been shrinking quite rapidly.

The last few years, we’ve seen resistance to a class of drugs called carbapenems. Ten years ago, carbapenems would be used only as a last resort. Today, carbapenems don’t work in treating [resistant] Gram-negative bacteria. There are very, very few options left for clinicians to deal with patients who have [resistant] Gram-negative bacterial infections.

And from what I understand, these Gram-negative infections can be pretty severe, right? These infections have high mortality rates.

Absolutely. So Gram-negative infections can be fatal if untreated — not always, but with a reasonably high rate of mortality. And again, in the context of poorer countries, when patients can’t even afford first-line drugs, they certainly cannot afford more expensive drugs, then they are much more at risk for dying.

In the U.S., we tend to pay for resistance through higher health care costs. In poor countries, we pay for resistance through more deaths. …

Can you recall and describe a little bit what happened when NDM [New Delhi metallo-beta-lactamase] appeared on the screen in India?

[In 2008], a patient who had traveled from New Delhi to Sweden was hospitalized for a Gram-negative bacterial infection.

The medical researchers then isolated the bacteria that was causing the infection. It was a Gram-negative bacteria, and it happened to have this new genetic variantal strain called NDM-1. They labeled it NDM-1, or New Delhi metallo-beta-lactamase-1, after the presumed city of origin, which was New Delhi. That was standard practice. That is what had previously been done.

Now, this raised a huge outcry in New Delhi and certainly within India, where it was seen as a Western attack on medical tourism in India. … The response to this was largely around the name NDM and not so much to the idea that here was a new bacterial strain that could harm patients in India, which really was the main concern for many people in the medical community.

But because of the outcry, this was on talk shows; this was on mainstream media; this was in all the newspapers. It was absolutely impossible to have a sensible conversation about the problem of drug resistance, which was a legitimate problem in India. Subsequently, this has led to some positive developments in terms of a government policy on antibiotics and so forth, but that was not the way it started.

It sounds like it hit like a bombshell.

It absolutely was a bombshell. It was unexpected, and the strength of public and media response to this was unexpected.

From the way you described it, it also sounds like it is quite likely that this NDM supergene, this bug, was quite widespread by the time it was detected.

It’s hard to tell how widespread NDM was at the time it was detected. I’d be very surprised if that patient who had NDM was actually the first one to have had it. Certainly he or she could have gotten it from anywhere else, from a patient from a different country, a different city in India, but it was a scientific practice to name it after the city where it was first observed.

What was unusual and different about this?

… What was unusual about NDM was, first and foremost, that it was extremely fit, which means that it could be transmitted quite effectively without dying out. Second, it conferred resistance to nearly all the important antibiotics we had against Gram negatives, which is of concern because we didn’t have any other antibiotics. And third, there was a study which showed that bacteria could pass the NDM gene between each other, even out in the environment, and not necessarily only in a patient’s body. …

Can you tell me how it works?

If you can think of this as if you go to the library and you check out a book that tells you how to do something, maybe to do some woodwork. Now, let’s suppose that you can return that book to the library, and some other person can check that book out and learn the same thing without ever having met you. That’s really what NDM is.

It’s basically information on how to be resistant to a wide range of antibiotics that are used to treat Gram-negative bacteria. They ride on a cassette called a plasmid, and the beauty of this, from a scientific perspective, is that completely unrelated bacteria can share plasmids and therefore gain knowledge on how to be resistant in the same way that any of us can check out a book from the public library and without ever having written that book, we can have access to that information.

That’s what makes it extremely dangerous, that it’s public information to bacteria on how to evade our best antibiotics.

Are you telling me that the bacteria are actually sharing information about how to avoid antibiotics? Is that what’s happening?

That’s amazing, but that’s really what’s going on. They are freely sharing information on how to deal with the antibiotics that we’re throwing at them.

And what’s the consequence of that? Does that mean that bacteria that normally we could kill with antibiotics are now becoming resistant just because they got the book?

What is going on is that bacteria, even if those have not been directly treated with the antibiotic, are still able to borrow genetic information on resistance from other bacteria.

They’re sharing the genetic information.

They are actually sharing the genetic information. …

Why is that environmental factor important?

The environmental factor of transmission of resistance genes is important, first from a scientific standpoint, that we didn’t realize that this could be done quite so easily; but second, it also meant that in places where water and sanitation was poor, where there was going to be lots of bacteria sitting next to each other, that you could have very rapid spread of resistance information across unrelated bacteria, just out there in the environment, which is a hugely greater risk than if it were only to happen within the bodies of patients who had these infections. …

So you’re saying that the bacteria were swapping this information just out there on the street without being in a person.

That’s correct. So they could transfer resistance genes even when they were in the same puddle of water, and they didn’t have to be in the same person. …

So why should we care? Is there something dangerous about this swapping going on in the environment?

The swapping going on in the environment is, first of all, unusual from a scientific standpoint, but also because there are far more bacteria in the environment, so the potential for a different specie of bacteria to gain information on resistance is much greater in the environment because there are so many different kinds of bacteria around.

Within the human body, there’s probably a more limited number, and therefore the potential for transfer of resistance genes is therefore less.

So we create a kind of a big pool of them out there that’s still a threat to human health?

You have to remember that although we’re human beings, we all live or share the same community with bacteria. We have probably 10 times the number of bacterial cells in our body than human cells, and therefore we’re sort of this continuum of bacteria that continues from you to me, out into the community and overall. This is really like an ecological problem where these bacteria collectively know how to evade antibiotics. That’s the nature of the problem. It’s an environmental problem.

It’s an environmental problem as compared to what?

It’s an environmental problem compared to your having heart disease or my having arthritis, where what happens to me doesn’t really affect outcomes for you. …

So how widespread is NDM?

Doctors are now observing NDM-1 all over the world. If you go to South Africa, doctors will tell you that they’re seeing a lot of NDM-1. There’s a lot of NDM-1 in Vietnam, and certainly many studies describing this in hospitals in India. So it’s getting to be quite common all around the world, which speaks to what a robust and fit pathogen this is. …

Let’s talk a little bit about India itself. What kind of factors might be driving resistance? What are the things that have happened in society, in past practice? Why is resistance growing so much in India?

There are probably three reasons why resistance is growing in places like India.

The first is, when antibiotics were introduced in the West — take the United States, for instance — the bulk of infectious disease mortality had already been reduced through chlorination of water, through establishment of public health departments and all sorts of other things which made sure that people were not dying of infectious diseases. And then we introduced penicillin, which was sort of the icing on the cake. It wasn’t the cake itself.

That’s not the case in countries like India and many other Southeast Asia countries, where a bulk of that infectious disease burden has not yet been reduced through water and sanitation and hygiene, and we’re really relying on antibiotics to do the heavy lifting there in dealing with infectious diseases. So there’s a lot more treatment of infections just because there’s a lot more infections there to begin with. That’s the first thing.

The second is that people in these parts of the world are getting much wealthier. Indians have [become] economically much more prosperous now than they were 10 years ago, and per capita, usage of many kinds of antibiotics of India have doubled, in some cases even tripled over just the last five years. That’s basically prosperity driving antibiotic use. That’s not necessarily a bad thing, because many people in India previously never had access to antibiotics, and now they are gaining access, so this is a good thing. But the overuse is a bad thing.

The third issue in India is really the easy, over-the-counter availability of antibiotics without a prescription. Now, certainly that is true in other parts of the world as well, but because of the size and skill of India’s pharmaceutical sector, which makes a lot of these antibiotics, they truly are available much more freely and cheaply in India than they would be in other parts of the world, and this is a third important piece of the puzzle. …

How should we think about the danger in the United States?

Drug resistance has been in the United States for a very long time, so those who watch the media think, well, this is an evergreen issue. I keep seeing this every year. What’s the big deal here?

How do you answer that?

The big deal here is that resistance has been steadily increasing ever since antibiotics were introduced in 1942. The first strains were noticed just a few years after in patients. The first resistant strains of antibiotic ever were noticed in vitro, which means not in humans but really in petri dishes two years before antibiotics were ever introduced to the population.

So we’ve lived with resistance for a long time, but what we have not lived with for a long time in the U.S. is really this idea that you would see patients who could not be treated with any antibiotic that was available to the doctor, and therefore that patient would have to either recover on their own or die. That’s a problem, because we’re now seeing patients who are sicker, who are immunocompromised and therefore at much more risk of dying without the antibiotics, and the combination of that with the drug resistance means that a lot of people are actually dying of drug resistance.

People often called these wonder drugs and miracle drugs, and now we have very sophisticated kinds of medical procedures that require very difficult things, like transplants and stem cells and so on. Do you agree with those that think that this resistance is some kind of threat to modern medicine?

Antibiotics are really the bedrock of modern medicine. You could not do many procedures without the ability to keep the [patient] free of infection. All of the surgical procedures, you know — you can’t do seven heart surgeries if you didn’t have effective antibiotics.

We don’t really have a substitute for effective antibiotics for as far into the future as we can see. Nobody knows what the substitute is going to be for antibiotics. We have vaccines; they do reasonably well with viral infections. Very few vaccines for bacterial pathogens. …

We clearly need new antibiotics, and we also need to find ways to perhaps recover the potency of existing antibiotics, and that has been done in the past through combinations of drugs.

So when a drug stops working effectively, we’ve had to combine with a different antibiotic so that they might work synergistically, and that might be a good, effective antibiotic to have.

But we have a real crisis in terms of having very few new antibiotics in the pipeline. Many of the large drug makers have left this area, and the few that remain are truly struggling. …

Dr. [Margaret] Chan, the head of the WHO [World Health Organization], said we may be entering an era after antibiotics. [The head of the Centers for Disease Control and Prevention (CDC)] Dr. [Thomas] Frieden said “nightmare bacteria.” What does this mean for the average person?

Well, for the average person, they should talk to their grandparents or great-grandparents if they have them around, to ask what life was like before antibiotics. Before antibiotics, if you were sick, you had very few options. You probably had chicken soup, and you rested in bed and hoped to get better.

If you take the first patient who was ever treated with an antibiotic, this was a policeman in Oxford … who was working on his garden on his day off from work. He was scratched on the cheek from a rose thorn on the rosebush that he was tending to, and the rose thorn scratch became infected with Staphylococcus aureus, a staph we know quite well now. It got infected; it became an abscess; the face got swollen; the infection spread to other parts of his body.

So about three months later — this was in probably February of 1941 — he was on the verge of death, and he was administered some penicillin. He got better on day one, day two, day three, day four. He was getting much better. The doctors could see that he would live, and then they ran out of penicillin, and he died.

Are you suggesting that we could be going back to a time when a scratch could be deadly?

We are perhaps already in a world where a scratch could be deadly, if you happen to be someone who can’t afford very expensive antibiotics and happen to live in a developing country. So the post-antibiotic era is not in the future for many people. It’s already here.

And part of this is because of resistance.

All of this is because of resistance. If we had effective antibiotics to treat infections, generally the antibiotics work really quite well. Infections like pneumonia are very easily treated with antibiotics. But when you don’t have effective antibiotics, then it’s a whole different story. …

So in some ways, this is a problem of the age of globalization.

This is a problem of shared commons, so just like each of us could choose to drive a car, and that contributes to global warming but we don’t really see the connection, in the same way, we could choose to overuse antibiotics in our own lives, and that has global consequences.

It seems, though, that you’re suggesting it may be a global problem, but that the solutions are different in different places.

That’s absolutely right. The solutions are very different in different places.

What do you mean by that?

In China, the important reason why antibiotics are overused in hospitals is because much of hospital revenues are derived from the sales of antibiotics, other drugs and diagnostics, so it’s part of the business model. If you’re in a hospital, you sell antibiotics. For many hospitals, that’s a quarter of the hospital’s revenues.

In India, the challenge is over-the-counter sales of antibiotics, especially very powerful ones.

In Kenya, it’s a problem of increasing use of antibiotics in livestock and the fact that you know herders will just give antibiotics to the animals quite freely.

In the United States, again, it’s a problem of huge amount of antibiotics being used for growth promotion in animals and also of large numbers of antibiotics being used in medicine itself.

So in every country, both the drivers of resistance as well as the incentives for people to overuse antibiotics are really quite different. So we need to find some local solutions here. …

You’re saying this is a risk to human health, right? This is something that anybody could get. It’s not some specialized thing.

Fifteen years ago — there’s a bug that we’re now very familiar with, methicillin-resistant Staphylococcus aureus — you could only get MRSA in a hospital. You would never get that riding the subway or in a gym locker or from someone else.

That has changed. About 15 years ago, it started transmitting within the community, and now the community epidemic of MRSA are at least as common, even if not as severe, as health care-associated MRSA. No one could have predicted that that would have happened, because MRSA was a health care-associated infection back then.

So it jumped out into the street, is what you’re saying.

It jumped out into the street, and you can now get MRSA easily just going to the gym locker, and you could get it from someone else.

You can be an absolutely healthy person and get MRSA. It’s an equal opportunity bug. You don’t have to be old and sick and dying in a hospital to get MRSA. You can be young. You could be an athlete, and you could be dead in 48 hours from an MRSA.

So when you have Gram-negative bacteria that also cannot be treated, there is no telling where these bugs can then move to. And if and when they move to being community infections, then we face some serious trouble then. …

… What should we do about this? What should governments be doing? What should industry be doing? What should medicine be doing?

There’s a lot that government could be doing, to start off with. A lot needs to be done on changing social norms and awareness about antibiotics. If you walked into a doctor’s office in Sweden and said, “Doctor, I’m not feeling well. Could I get an antibiotic?,” they would look at you as if you are crazy, because the norm in that country is that you go into a doctor’s office, and they would not give you an antibiotic, and they might give you one three days later if you’re still sick.

Now, we know that the situation in the United States is really quite different, that antibiotics are often prescribed on the very first visit. Changing that norm is really your very first role of government to play.

That’s practice, right, how we use them?

Exactly. So if people don’t realize that every time they take an antibiotic, they’re causing this huge societal problem as well as a problem for themselves and their kids, they might use them very differently. But guess what? Most people don’t know that that’s a problem.

What else?

Certainly government could be encouraging better use of antibiotics in hospitals by, first of all, encouraging hospital infection control.

In many hospitals, antibiotics are used to treat patients before infections that could have easily been prevented, and that’s natural, because you’re asking hospitals to spend money on infection control that they don’t get reimbursed for. Or they could treat patients with antibiotics that they could get reimbursed for, and guess what? They prefer to treat patients. So changing that calculus to prevention would be a very important thing to do.

One of the most important things that has happened in this country … over the last seven or eight years has been the introduction of a vaccine against pneumonia. So the pneumococcal conjugate vaccine that’s now given to all kids across the country, that’s made an enormous difference in reducing the consumption of antibiotics. So again, the government has a role in perhaps helping fund vaccines or research through NIH [National Institutes of Health] to figure out how best to prevent infections before they actually occur.

Then certainly there’s a role in trying to help get new antibiotics produced, but not just to pay for new antibiotics from pharmaceutical companies, but to pay for antibiotics in a way that will ensure that these drugs will be used appropriately in to the future.

When a pharmaceutical company now comes up with an antibiotic, guess what? They want to sell as much of it as possible because they have to make profits for their shareholders, and that’s appropriate. That’s completely appropriate to the incentives the way we’ve set it up for them, but not appropriate to what’s good for society.

Do you get the impression that this issue of resistance is a top priority in the United States government?

The issue of resistance is nowhere near the sense [or] the kind of priority it ought to be in the United States government. …

If you view government’s commitment to a problem at least by the amount of time and money it spends on it, it’s clear that the government doesn’t see this as a problem.

And as a priority?

Certainly not, in spite of the recognition at the highest levels of the public health service — from Dr. Frieden and others — that this is something that they should take quite seriously.

It also seems that there’s a lot that we don’t understand or know about the scope of resistance. I’m not talking about the science now, but I’m talking about the data. Do we know how many people get sick and die? Do we know how many bacteria are resistant?

… What we do have on drug resistance are data that show a fairly systematic increase in drug resistance. That data is pretty solid. It comes from both government as well as private sources, and it all points to the same direction: Drug resistance is actually getting worse.

Do we have data that shows the effect of drug resistance on people dying? Not as much as we would like. And that’s for a very practical problem, because patients who get drug-resistant infections also have to be sicker. So the fact that someone is more sick and also had a resistant bug doesn’t necessarily mean that one caused the other. It’s a little trickier than just saying someone died of HIV, which is much more direct.

That I understand. But isn’t there also a problem that we don’t really have a surveillance in place for resistance?

Many years ago, the United States decided to take the problem of fisheries seriously in the U.S., and there was an act called the Magnuson-Stevens Act, which was intended to protect the fisheries along the coast of the United States as a national resource that was vital to the country’s well-being. Huge amounts of money — hundreds of millions — were spent on surveillance, on research, on quantifying the problem and addressing the problem.

Here we have another natural resource of the same magnitude of importance, antibiotic effectiveness. What we really need to see is something like a Magnuson-Stevens Act, which says we need to spend that quantum of money on surveillance, on knowing the status of antibiotic effectiveness, where the antibiotics are getting used. We have no idea how much antibiotics are getting used in animals, for instance. Almost no idea. All of this needs to get reported if we really want to take the problem of conserving this resource seriously.

So there’s not a lot of reporting; that’s what you’re saying at the core.

There’s no national reporting coordinated by the government in a broad way to deal with drug resistance.

…Why is there no public outcry about resistance?

It’s puzzled me why the public doesn’t speak out more on resistance. There are certainly survivor groups. There are MRSA survivor groups, and there are civil society organizations dealing with drug resistance. …

A lot of people don’t know that they died of drug-resistant infection. This is a hidden epidemic, and it hasn’t risen to the forefront where people recognize, “Yes, my grandfather died because of a resistant bug,” or, “My sister died of a resistant bug.” When we have better information on this, I think we’ll have public advocacy, but we don’t have that right now.

Why do you say this is a hidden epidemic?

It’s a hidden epidemic because there’s nowhere on your death certificate that would say that such-and-such person died of an infection that could not be treated. And if it’s not a cause of death, then it’s not something that people recognize [as] something that actually killed them.

And is it also hidden because doctors in hospitals and governments don’t talk about it?

Well, because the data is so poor, there is not enough of a conversation about the extent of drug resistance, although all the data that we do have suggests that it is going up and has been going up for quite sometime now.

Certainly hospitals have no incentive to tell patients that they have high levels of drug resistance. And similarly, which doctor would really want to tell their patient that their infection was untreatable and that they were running out of options?

They don’t like to talk about that.

This is not something which typically happens in a hospital setting or something that comes up as a conversation that because of the pathogen that you probably picked up at the hospital, you’re probably going to die because we can’t treat the pathogen. That’s not a pleasant conversation.

If we don’t know how many people died from this, how do we get people to care about it?

Quantifying the scale of a problem is something we spend a lot of time thinking about and worrying about, and it’s absolutely important to quantify the scale of the problem. In fact, Sen. Ted Kennedy [D-Mass.] had said when he used to think about drug resistance — and it was something he was totally aware of — he said many times: “You have to quantify the problem. If you can’t quantify the number of people that are dying or the economic cost that it imposes, there is very little that we as politicians can really do about it.” And that’s absolutely right. But we haven’t had the data or the research to really support that sort of quantification.

It sounds like you’re saying we have public policy paralysis because we don’t have data, and we don’t have data because we have paralysis.

If people were dying on the streets because of drug-resistant infections and had a big X on their foreheads which said that they had drug-resistant infections, trust me, there would be policy action.

But because these people are dying of infections and they already are sick from other conditions, there is very poor recognition that this is a problem, and therefore there’s not the impetus to get the quality of data that could then show that they died of a drug-resistant infection.

On this very point, there’s been a large number of serious studies for 30 years about this. The Fogarty commission, the Institute of Medicine, Office of Technology Assessment, major studies, hundreds of hours — these studies are sort of stacked up and yet not acted upon. What does that say?

The problem of drug resistance is a complex problem. It’s fundamentally not a medical problem. It’s a problem of incentives that none of the actors in the system — whether they’re physicians, patients, pharmaceutical companies, hospitals — have an incentive to try to solve the problem on their own.

Physicians don’t care because they don’t really bear the consequence of resistance, and it’s easier to give out an antibiotic when they’re asked for one. Patients don’t care because the consequences of taking antibiotics fall to everyone else. Hospitals don’t care because someone else is going to pick up the bill, even if the patient has a drug-resistant infection. And pharmaceutical companies don’t care, except if it actually creates a market opportunity, in which case drug resistance could even be a good thing.

We don’t have government watching out to protect what should be declared a vital natural resource. So unlike other problems where there are stakeholders who do care, here is a major national problem and an international problem where there are no stakeholders willing to step up and say, “We’re being affected by this, and therefore there ought to be a solution.” That’s why we’ve had lots of reports but very little action.

… Is it possible that what we really have here is a failure of the market?

There is a market failure in two ways: There’s a market failure in the sense that individuals impose what economists call an externality on other people, which is we use antibiotics too much, and therefore we mess up the drugs for other people. So that is one form of market failure.

The other form of market failure comes from the supply side, which is that there is a problem of reimbursement, which is health payers are unwilling to pay very high prices for antibiotics. Why? Because they’re used to paying pennies a dose for penicillin, and the idea that a new drug should cost maybe $5,000 just doesn’t seem right to them, although they’re willing to pay that kind of money for someone to save them from cancer.

But if you think about it, we should be willing to pay large amounts of money to protect us from dying of infectious diseases, just as we should from cancer, but there is a real reimbursement problem here, and therefore not enough antibiotics actually get made.

You call it reimbursement, but isn’t it really a third-market problem here, that the pharmaceutical companies don’t see the return on investment so they just won’t make these drugs? They would rather make something with big blockbuster profits?

The pharmaceutical companies, if they were allowed, I think, to charge a lot of money for an antibiotic that would be used sparingly would be willing to make a drug, because they care about the profits, and currently they don’t want to make the drugs because they feel that they can’t charge large amounts of money for antibiotics.

Now, high prices of new antibiotics should not really be a problem. It’s just a signal from nature to us to say, look, there is nothing in the Bill of Rights which says that you have access to cheap antibiotics and effective antibiotics for as long as this country exists. There is no guarantee. So just as we run out of oil, we should expect to pay more for gasoline, as we run out of antibiotics, we should expect to pay more for antibiotics. That’s just the way it is.

Is that realistic in today’s environment?

It absolutely is realistic, because if we face high prices of new antibiotics, maybe we’ll be a little more careful about how we use the existing ones.

What does that mean in the developing Third World?

In the developing world as well, if governments were aware that they were going to be facing high costs of new antibiotics, maybe they would take much greater precautions about existing antibiotics.

So in a sense, the problem in the U.S. is one of affluence. We can afford to buy antibiotics, and therefore we do, and a lot of the problem in the developing world is of ignorance. Same outcome, but it comes from a different space, where governments have not really recognized that this is an important problem that’s really going to bite in a few years and cause some very serious consequences.

Seriously, where is this whole problem headed?

As we run out of antibiotics, undoubtedly there will be some pharmaceutical companies that do come out with new antibiotics. They might be very expensive.

Where we’re headed is a continuation of the current path, where we end up paying a lot more money for new antibiotics and we probably have more people dying of infections, but hopefully this will spur better infection control in hospitals, because no one wants to incur the costs of those highly priced antibiotics. There are many parts of world where people will unfortunately die because they can’t afford these antibiotics.

But where are we headed with the problem of resistance?

Resistance is an evolutionary phenomenon, and therefore resistance is probably going to keep going up for some period of time, but it depends on how much more antibiotics we actually throw at the bacteria. If we substitute the current antibiotics with new ones or different ones, it’s possible that resistance to some of the existing antibiotics may actually go down over a period of time. So it’s all an ecological game, and it depends on how we play it.

Were we wrong to call them miracle drugs?

They truly are miracle drugs. The idea of a drug that you can take inside your body which is a living organism, to specifically kill other living organisms inside your body — now, that’s special, and that’s a miracle.

But resistance is sort of the underside of the miracle, isn’t it?

Resistance is just a natural consequence of control of any biological agent. We have resistance when we use too much herbicides on our lawns. We have resistance when we use too much insecticides on pests. We have resistance in HIV and tuberculosis. Any attempt to control a biological agent will result in resistance, and bacterial infections are not any different.

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