Dr. Brad Spellberg is an infectious disease specialist and leader in the field of developing ways to combat drug resistant infections. Spellberg, who wrote a book about the problem, Rising Plague, told FRONTLINE that the science of developing new tools in the fight against infection is in trouble, unless the culture around developing drugs changes. This is the edited transcript of an interview conducted on May 30, 2013.

Can you give me a very brief explanation of the discovery of antibiotics and what the significance of that was for public health and for modern medicine?

In the pre-antibiotic era, doctors were taught in medical school that they should admit to themselves they could not change the course of their patients' illnesses. They had no interventions that could really change things. Their job was to make an accurate diagnosis so they could give an accurate prognosis to the patient.

When antibiotics came along, it totally revolutionized things. It gave us an intervention. It allowed us to actually treat diseases. It was an overnight flip of the switch, where all of a sudden you went from, "I can't do anything about this, but here's what you have," to "Here's what you have, and I can make it go away." And that opened doors to all kinds of new avenues in medicine.

So when you say this opened the door to all kinds of new avenues of medicine, what do you have in mind?

You know when you've got antibiotics that treats or prevents infections, [so] all of a sudden you can do complicated surgeries that you couldn't do before. You can do organ transplantation, which you couldn't do before. Cancer chemotherapy - you wipe out the patient's bone marrow, they get infected and die, but if you have antibiotics, you can actually save them, so you can actually give the chemo. Premature neonates, all kinds of areas of medicine were opened up. ICU care was opened up because of the availability of antibiotics.

Can you explain to me resistance, and how did that come about?

Antibiotic resistance has been with us for millions and probably billions of years. Resistance is just the bacteria not dying from the antibiotics that they are exposed to.

Antibiotics are bacterial weapons. They have been waging war among themselves for billions of years with these weapons, and if they're going to make the weapon, they have to learn how to resist it so they don't kill themselves. In nature, widespread right now is a lot of antibiotic resistance to drugs we haven't even invented yet, but they already know how to resist.

And this concept of resistance was aided by the creation of this sort of manmade set of antibiotic drugs, right? You described natural resistance, but then there was a period in the last 70 or so years where we did it.

I think the difference really is the amount of antibiotics that the environment is exposed to. It's not that there's different mechanisms. We're not creating the resistance. The bacteria have created the resistance, but we don't notice the resistance. It's at low levels in nature.

We start dumping thousands and thousands of kilograms of antibiotics into the environment, millions of kilograms into the environment, and all of a sudden all the susceptible bacteria die off. What's left behind are the pre-existing resistant bacteria to grow and replicate and spread their resistance, and now it peeks above the water level, and we start to notice the resistance.

But we had something to do with this, right, through the overuse of antibiotics and maybe the carelessness with them?

The more antibiotics we use, the faster resistance spreads. It's simple Darwinian natural selection.

Was there a moment when you came to this realization about resistance? Tell me a little bit about your own personal discovery.

Antibiotic resistance is something that all infectious disease practitioners think about, know about and deal with. But the moment I guess where the power of the resistance was brought home to me was when I was a fellow in training and for the first time encountered a patient that was infected with bacteria that was not treatable, that was resistant to every antibiotic we had.

Do you remember that moment? What was it like?

... This was a young woman who had leukemia, and she had gotten an infection, and you look at this computer screen, and what you see on the computer screen, or what I saw, was all the names of the different antibiotics we have, and then next to the names [was] "R" for "resistance" - R, R, R, R, R. And I kept looking down going, "Where is the 'S' for 'susceptible'?" But there wasn't any "S" for "susceptible."

And so what do you say to that patient's family member? There was nothing I could do. That was a very difficult conversation.

How did you feel then?

Sort of astonished that in the 21st century we could run out of drugs, that we had bacteria running around that had developed resistance to everything. We had nothing left. It set medicine back 80 years functionally.

One of the more recent developments has been the rise of a group of [bacteria] known as Gram negatives. Can you explain to me what they are and why this is such an urgent problem?

Gram negatives is a class of bacteria, or a group of bacteria. It's not so much that the bacteria know that they're Gram negatives; it's that we have a stain called a Gram stain, and if it stains the bacteria purple, we call them Gram positive, and if it stains them red we call them Gram negative. That has to do with the structure of their cell wall.

By and large, the Gram-negative bacteria are the masters of resistance. They're the ones that develop it the fastest, that spread it the most rapidly, and they are the ones that right now we can't treat, that we've run out of antibiotics to treat.

When you say they're the masters of resistance, what do you mean? What happens?

They have thousands of different ways to cause antibiotic resistance. Lots of them are mobile or transmissible, so they can share them with each other. They can give them to other bacteria, so when the first one learns how to become resistant to an antibiotic, very quickly thereafter all of them in the neighborhood know how to do it. That's what I mean by masters.

And why are they such a threat to human health?

If you look at the impact that antibiotics have had on human health, it is a dramatic increase in life span and a dramatic improvement in quality of life. You are no longer dying as a child, as a teenager, as a young adult of mundane infections. We consider them mundane today. They were lethal back then, before antibiotics, so it revolutionized the social patterns that humans deal with.

We live longer; we're healthier. And when you don't have effective antibiotics, that's what's at risk.

I was thinking specifically about these Gram-negative bacteria which seem to be evolving resistance now. Why are they such a threat?

I think we need to get past the idea that antibiotic resistance occurred in the era of antibiotic discovery. Antibiotics were invented by bacteria. We discovered them; they invented them. Resistance is not a new phenomenon. It's been around since the first bacteria invented the first antibiotic probably billions of years ago.

What is different is the rate of spread because of the selective pressure we applied when we use antibiotics and put them in the environment. And the Gram-negative bacteria can simply adapt remarkably quickly. I have watched some of these pathogens develop new resistance in the middle of a course of therapy.

Just within days?

Within days.

That means that that antibiotic has basically stopped working while you're treating the patient.

The way you know that the resistance has emerged in the middle of a course of therapy is the patient is very sick. You start the antibiotic; they get better. On day three or four, all of a sudden they get sick again, and back comes the same bacteria that you thought you eradicated. And now when you sent it to the lab, instead of "S" for "susceptible," it says "R" for "resistance."

So what do you do, switch to another and another?

If you have another, you switch to another.

... What was the role of antibiotics in the modern pharmaceutical industry?

I would say that the pharmaceutical industry was founded upon antibiotics. Sulfonamides, which came around in the late '30s, are really the first blockbuster drugs that sold in mass quantities and led into penicillin, which was the miracle drug that everybody knows about. And really, many pharmaceutical companies made their bones on making and selling penicillin.

The concept of drug discovery and the way that pharmaceutical companies discover new drugs and screen was invented by Paul Ehrlich, who was trying to discover antibiotics at the turn of the 20th century. So I think antibiotics led to the pharmaceutical industry.

One of the companies that was very prominent in that period was Pfizer. What was their historical role in this period of the early discovery?

Pfizer was one of the first manufacturers at large scale of penicillin, figuring out how to ferment the mold that makes penicillin and produce it and purify it at large scale, so they've been around the penicillin game since the early '40s.

As a company also, wasn't it very important in their growth?

I don't have the exact numbers, but penicillin was this miracle drug that was sold in vast quantities and many pharmaceutical companies, really made them.

And also wasn't this a time of great expansion in the use of medicines and drugs and antibiotics? In other words, we sort of created a pipeline here.

Before antibiotics, there were three drugs in the entire pharmacopeia that doctors have. They had morphine; they had very impure forms of insulin; and they had digitalis for heart failure. That was it. None of them really were lifesaving; none of them changed the practice of medicine.

Then antibiotics came along, and it was a literal revolution. You cannot overstate the change overnight with the availability of these drugs. It revolutionized medicine. It made medicine an interventional field where we could make people better, not just a monitoring field where we would tell you what you had and then give you a placebo, which was often booze. Many of the treatments that doctors used before antibiotics were alcohol-based because they made people feel better.

And this explosion then brought big companies like Pfizer to the fore, right? Didn't they ride this period of expansion?

I would say from the 1940s through the early 1960s there was a literal explosion of new antibiotic discovery. Nobel Prizes were won; companies made lots of money. There was a strong industrial base to discover new ones and produce them.

Could you explain to us a little bit your own role with Pfizer, the committee that you served on?

I was on the therapeutic area Scientific Advisory Board with Pfizer for, I don't remember, one or two years or something like that. ...

The job of the advisers was to help the scientific team at Pfizer select which molecules looked most important and to figure out how they should be developed in a way that would best serve the public.

At that time, did you feel that there were molecules coming or there were promising things that you were looking at?

When I joined the advisory board at Pfizer, I felt that their pipeline was probably the most comprehensive and important antibacterial pipeline in the world. ... They had, I think, the deepest pipeline.

Now, these were early-stage molecules by and large, but the deepest pipeline and some very, in my opinion, very impressive molecules that could have done a lot of good had they been developed.

And what was the nature of Pfizer's commitment in terms of the kinds of research team they had there?

Pfizer had a world-class antibacterial research team, maybe even the best in the world.

How did you know that? Just by talking to them? By reading their research?

You see the work that they're doing, that they're presenting to you. You see the work that's being presented at meetings. You look at the types of molecules they are discovering, the types of drug candidates that they're working on. And you look at the pedigrees of the scientific team.

You told me that they had a lot of promising compounds. ...Do you remember how many? Is there any way to quantify what was happening at that time?

I would say that there were a number of, in my opinion, very promising and what I recall very important drug candidates that were not focusing on "me too" areas of infection but were focusing on the types of bacteria that we're really having severe problems with right now, the highly resistant Gram-negative bacteria.

And when you say "promising," again, just help me understand that. What does that mean? ...

I think you know that drug development is a risky business even in the best of circumstances, so you can't look at a drug candidate before it goes into people and say this is a sure thing.

When I say "promising," the drugs have characteristics that made me and the people that I was working with believe that they had a good shot at development, and most importantly, that they hit the types of bacteria where there is huge unmet need. ... These would have solved problems and saved lives had they been successfully developed.

So at some point when you were doing this work, Pfizer decided to change direction. Do you remember when you heard about that?

Yeah, I do. I was called by a friend and colleague who told me that he had heard a rumor that Pfizer was outsourcing its antibacterial division, and I told him that's impossible; I'm going to an advisory board meeting in a couple of weeks, so you can't be right about that. And he was.

What did he mean by outsourcing?

The announcement from Pfizer that came was that they were going to move their antibacterial division to China, and the scientific team was highly unlikely to move to China, so what that meant was that they were going to have to find a new team and a new physical plant to set up in China to house the research.

... What did you think of that?

When I saw the press release, it seemed to me that this was a harbinger of them getting out of the business, and the reason why was almost all the other big companies had already gotten out of the business, and it was something I had actually been worried about when I first joined the Scientific Advisory Board.

The reality is, it probably was smart business to get out of the business. It is not a good economic model of investment for countries to invest in antibiotic development. The economics are bad; the regulatory risk is high; the science is difficult.

So if you look at it from the perspective of a for-profit company that answers to shareholders, they are probably doing the right thing for their shareholders. It's just that we have this societal problem that perhaps is not best served as a society when we look at what is the best thing for individual for-profit shareholders.

In this case they said they were going to move the team to China, and then really that didn't happen, right?

They were going to move the program to China. The team was never realistically going to move to China. You can't pick up dozens and dozens of scientific experts and ask them to move their families to China.

... It seems to me that if they're going to switch teams, that put at risk a lot of the things they were working on.

At a minimum there was going to be a substantial delay in development. That's assuming they could get a very skilled team in place in China that could eventually shepherd the molecules forward, the drug candidates forward.

But the reality is that what we have seen as companies leave the field is a massive brain drain, a loss of tremendous expertise that very talented scientists developed over time in figuring out how to discover and develop new antibiotics. And when those teams break apart and the individuals get reassigned or leave the company and go elsewhere, that is a loss, a brain drain that is going to take years to decades to recover from.

So it's a loss to society.

That's correct.

So you remember when you heard about this, there was a dinner you described, all of your committee members. Tell me what that was like.

It was the last advisory board I was at. We all went out to dinner with the scientists, and I would describe it as the equivalent of an Irish wake. It was a lot of depression. There was a lot of scientists that had dedicated their lives to working on drugs that they felt were critically important for society and would save patients and help patients.

The scientists, they're not in it for the money. They're not making millions of dollars a year. These are professional scientists that want to make molecules that treat patients, and they felt like the rug had been pulled out from under them.

You describe some economic reasons why companies make these decisions, but I'm wondering if at the Irish-wake dinner, did the scientists have any sympathy for that argument?

I think when you're in the middle of that kind of a thing where you've dedicated your life to a certain set of principles, been working on things that you think are very important, it's hard to have sympathy for business concerns.

But the reality is, if we want to solve this problem as a society, pretending that the business concerns are not real or important is not going to help us. We have to deal with the fact that there are real, legitimate business reasons why companies have gotten out of this business. If we want companies in this business, we need to figure out what those reasons are and reverse them. ...

... So what's happened to these compounds now? Where are they?

I do not know.

It's possible that there are promising compounds still sitting there, could be further developed?

The molecules exist. I have not seen publicly released reports of their development, so I think that it is reasonable to assume that what you said is true, that there are molecules sitting on a shelf, not being developed, although they may be developing it and not releasing public information. ...

... How typical is this Pfizer episode for the larger question of the industry and the future of antibiotics? ...

This is the rule. This was something a lot of us had been worried about. Twenty-five years ago there were more than 25 large companies working to discover and develop new antibiotics. Now I would say there's two, maybe three, and Pfizer was the most recent casualty of a convergence of difficult science, very unfavorable economics and a regulatory environment that was not only not nurturing but suppressive.

So what you're saying is really that the public is being hurt because of the bottom line, because of these calculations about return on investment. Twenty-five years ago, were companies as concerned about the bottom line? Why could they do it back then and not now?

... The low-hanging fruit of antibiotics has been plucked. The stuff that's easy to be discovered has been discovered, and each new generation that you need to come out with to stay one step ahead, because resistance never stops - it's inevitable, and it will always be there - you need to be on that treadmill. You need to be constantly staying one step ahead. The science, each time you have to take the next step, is more difficult, more expensive.

The economics have gotten much worse. The costs of development have skyrocketed. The return on investment has not improved, and the regulatory environment today versus 15 years ago is much less favorable for antibacterial development.

Some people say it costs a billion dollars to develop a new drug all the way. So what you're saying is, companies are just much more reluctant to sink money or to take a gamble like [that].

When you talk to people who work in big companies, the scientists, they tell you that their competition is not the other company; it's the other divisions in their company.


Because there is one stream of R&D, research and development, dollars, and if you want your program to get funded by those dollars, the company needs to prioritize the money to you and not to the other division.

So here is a large company saying:
"I can make billions off cholesterol drugs, blood pressure drugs, arthritis drugs, dementia, things that I know patients are going to have to take every day for the rest of their lives. Why would I put my R&D dollars into the antibiotic division that isn't going to make me any money when I can put it over here [in a division] that's going to make a lot of money for the company? I answer to the shareholders. By law, I operate the business. I'm the business leadership. I answer to the shareholders."
Where would you put your R&D dollars?

It sounds like you're describing a situation, though, in which capitalism seems to be failing public health.

Antibiotics are unique drugs. They're not like any other class of drugs. Fifty years from today, the cholesterol drugs we have now will work just as well as they work today. The cancer drugs we have now will work just as well as they do today. That's true of all the other drug classes. Antibiotics are the only class of drugs that the more we use, the more rapidly we lose. When you use it, it becomes less effective for me, and vice versa.

They are a communal trust, they are a communal property, and we probably do need to start looking at different economic models and regulatory models so that we can get the molecules we need developed and protect them from overuse once they are developed.

Would these companies rush in if we raised the price of antibiotics to be like some of the other drugs that are very expensive? Is that the problem?

When you look at why the economics of antibiotics are unfavorable, the number one reason is they're short-course therapies. You take them for seven days, and then you stop. The number two reason is they're not priced competitively to other classes of drugs, particularly when you look at the power to save lives. I mean, these things cure the disease. The antibiotic cures the disease. It saves your life.

We're not comfortable as a society paying more than say $100, $200 for an antibiotic course, because we've been sort of spoiled by the penicillin experience. We're willing to shell out tens of thousands of dollars for cancer chemotherapy, but we're not willing to do that for antibiotics.

So yes, I would say pricing is one reason why the economics are unfavorable for antibiotics.

Do you think we find ourselves in this position because we were spoiled by the penicillin experience and maybe we were optimistic about what science could accomplish? We have a cultural problem here?

We do have a cultural problem, and in fact that cultural problem imbued the medical community for 40 years. When you look at the power that the antibiotics have by the late '40s and early '50s, you already had experts saying:
"We solved the problem. We've got antibiotics. We've got vaccines. Infectious diseases are done. We're good. Let's move on to other things."
And what they have forgotten was the warning that Alexander Fleming himself, the man who discovered penicillin, gave us in 1945: that resistance was already being seen, and the more we wasted penicillin, the more people were going to die of penicillin-resistant infections. And ultimately the resistance caught up with us.

... Is the government doing enough? Is the kind of action that we see up to the nature of the crisis?

When reporters like you ask me how many resistant E. coli infections do we have, it's pretty sad that I have no idea what the answer to that question is. It's not that the government agencies are not aware of the problem and are not doing anything. It's that we have not had a comprehensive plan for how to deal with antibiotic resistance. We don't have reporting mechanisms like they do in Europe to know where resistance is occurring. Who is using the antibiotics. Are we overusing them?

You're telling me we don't know the answers to the extent of the problem? We don't have the data?

That is correct, that is correct. I do not know how many resistant infections are occurring right now. I don't know what the frequency of resistance in different bacteria are. We do not have those data. They are not presented publicly. They are not gathered on a large scale.

There are pieces of data acquisition, but there is not a concerted, coordinated effort to gather the information and make it available. Nor is there a concerted effort to apply financial or regulatory constraints to overuse, either in humans or in animals.

I don't understand. What do you mean?

If we want people to not waste our antibiotics, we need to apply pressure to make people not waste antibiotics. It is so easy to use an antibiotic. The cost to the individual is so low. We need to begin to apply policies that recognize that these are a shared public resource and should not be wasted at a whim.

So that may mean that there are financial penalties for using too many antibiotics. It may mean banning antibiotics from being used in certain circumstances, whether it's in animals or in certain human circumstances, those kinds of policies we have not even explored.

... Is there also a problem that our politics isn't very responsive to this? There aren't patient groups, are there, advocating for these things? We see great outcries about cancer, about HIV/AIDS - certainly justifiable. Why hasn't that happened here?

One of the big barriers we've had to advancing policy change is that it's been very difficult to gather patients and their families to take to Capitol Hill to explain to politicians, and frankly to the public, how that problem is.

That's maybe in part because when you get an infection and you die of it, it's quick. You're not lingering from it. I think people have an expectation that you're either going to be cured or if you're not cured, well, nothing was going to save you, so what's the point of talking about it? And cancer, I think the emotional impact on the family is just different. The other part of it is that when infections are acquired in the hospital, hospitals don't want to talk about it.

Why is that?

Because you do not want to be perceived by the public or by regulators as the hospital that's killing people with infections, even though it isn't the hospital that's killing people; it's the bacteria that are very difficult to control.

But there is sort of a conspiracy of silence, not because anybody is doing anything evil or bad or wrong, but because I don't want to be the sacrificial lamb that first opens the conversation. Let the other hospital bring it up.

As a result, though, people don't know that there are these problems, right? Hospitals are reservoirs of these. The public seems to be in the dark.

I think that there has been some improvement in public awareness that if you need to go in the hospital, you need to go in the hospital, but you should try to get out of the hospital as soon as you can. Hospitals are where we concentrate the sickest people in society. We give the most antibiotics to patients in hospitals, and we poke holes in patients and put plastic in various parts of their bodies. Of course that's where the most resistant bacterial infections occur. It's expected.

We do need to improve our infection-prevention technologies and practices so we can reduce the amount of infections that occur. But the reality is we're never going to get to zero. ...

... So who in the government is in charge of policy about antibacterial resistance?

I don't know that anybody knows the answer to that question. There is what's called an Interagency Task Force [on Antimicrobial Resistance (ITFAR)] that was established in 1999 that includes many divisions or agencies of government, and I would describe it sort of as a nominal task force.

How would you describe it?

The task force is real. It exists on paper. It went through years where it did not meet. It has met rarely since, and there isn't anybody really who is singularly in charge of coordinating the efforts across these agencies so that there is a focused, an intentional strategy response to dealing with antibiotic resistance.

Nor is there an external body of experts who live at the front lines and know a lot about these types of infections, where they occur, how they present and how to deal with them. There is no such feedback mechanism for external experts to give input to the Interagency Task Force.

And this task force, how would you describe what it's accomplished over the more than a decade that it exists?

I would say that individual agencies within the task force, working on their own, have accomplished things but that the task force as a whole hasn't pretty much done a damn thing.

... What really needs to be done in public policy today that's not being done?

I think that we need to rethink how the economies of antibiotics discovery and development is done, how would companies make money doing this, because we do need a private component to discovery and development.

It's very expensive and risky. You need entrepreneurial spirit to come in and discover and develop drugs, but we need to figure out how to partner the public with private and create public-private partnerships to change the economics so that we can get the drugs we need discovered and developed.

So we need a new economic model basically, a new paradigm.

We need a new economic model, paradigm. The government - actually, that is one of the areas they have had success in. ... BARDA is the Biomedical Advanced Research and Development [Authority] and was established initially really to focus on encouraging the development of responses to biothreats, to possible bioterrorism agents.

Or biowarfare agents.

Or biowarfare agents. But over time, the definition of a biothreat has expanded to include antibiotic-resistant pathogens. And BARDA has the wherewithal and funding to partner with companies to get needed drugs developed.

I would describe BARDA and the NIH [National Institutes of Health] partner[ship] with BARDA, NIAID, National Institute of Allergy and Infectious Diseases, as the life support that is keeping the nearly dead body of antibiotic development going. They are what's keeping the heart beating right now.

I would say that is an area where the government has stepped up to the plate. It would be great if we saw an expansion of these kinds of activities. We also need to rethink how we prevent infections. We need to rethink financial incentives for using technologies.

If your infection prevention is based upon wanting people to change their behaviors, that's a tough row to hoe. We need technologies to make our infection prevention more effective. We need to stop wasting the antibiotics we have so that they last longer. We need to protect them. That means we need to think about the way we think about approving the antibiotics. We need to change the labels.

... I was struck by your statement that we don't have enough data. It would seem that's the responsibility of government, isn't it?

There has been a piece of legislation around for years that would create the kind of network we need to gather the data that we need and make it publicly available, both in terms of where resistance is accruing and how much antibiotic use is going on. It's called the Strategies to Address Anti[microbial] Resistance Act, or STAR Act, and it's never come up for a vote.

It is frankly embarrassing that we as a country do not know where resistance is occurring, how bad the problem is for various organisms, or who's using what antibiotics when. Europe has taken great strides to solve this problem, and we haven't.

Is industry doing enough?

I think all of us need to do things differently and better, so I think it's not fair for us to say to a for-profit company, we need you to act against your own self-interest and invest your money in this area instead of the other areas where you're making money. But it is reasonable for us to find ways to partner with them so that they are able to invest money in discovery and development of new antibiotics in a fiscally responsible way.

Are doctors doing enough?

I have been in the situation where I had a patient who probably didn't have a bacterial infection, and I have had to write prescriptions for antibiotics. What drives that, in my opinion and in my own experience, is fear. And it's not fear of lawsuits; it's fear of being wrong.

I cannot say with certainty when you come to me with complaints whether it's a virus or a bacteria causing the infection. And just one patient, it's just one prescription - how much damage can that one do? So what wins over logic is brain-stem level fear of being wrong and making a mistake. Can doctors do better at not prescribing antibiotics inappropriately? Absolutely. Should we do better? Absolutely. But again, if your policy is to depend upon changing human behavior, that is a policy with probably a low likelihood of long-term success. We need to give tools and technology to enhance the effect.

What do we need? We need rapid diagnostics. So when you come to my office, I run a test, and in 15 minutes I know if you have a virus or a bacteria. Once I see the printout [that] it's a virus, now I don't need to give you the prescription....

So you've given me a good list here. We need more data; we need diagnostics; we need a better model for drug development; we need to take care of the antibiotics we have. Is our government today focused on those things?

I would say there are pieces of government focused on pieces of the problem, and what we don't have is a coordinated response.

... How big a concern is the use of antibiotics in feed for animals and why?

I was shocked when I learned that 80 percent of the antibiotic use in this country goes to animals, not to people, and the vast majority of that 80 percent is to promote the growth of livestock, not to treat sick animals at the vet's office.

What if you sit here and talk about the need for doctors to stop wasting antibiotics? Let's pretend half of our antibiotic use that doctors prescribe are waste. That's 10 percent of the overall antibiotic use.

What about the 80 percent that's going into animals? We cannot develop meaningful policy to protect antibiotics if we ignore the 80 percent of the problem and focus only on the 20 percent of the problem.

But what's the problem? In other words, if we put so much antibiotics into the animal food chain, how does that affect human health?

When we expose animals and the environment to antibiotics, it goes back to what we said before. It is simple natural selection. The more tonnage of antibiotics you dump into the environment, the more you're going to kill off susceptible bacteria, the more you're going to leave behind resistant bacteria. Those resistant bacteria may be in the guts of the animals we're feeding antibiotics to, and when those animals are sold for slaughter, those bacteria can get transmitted to people.

It may be more complex than that. The animals poop; the fertilizer is used on crops; the poop gets into runoff. We create environmental reservoirs of resistance. All of this, these resistance mechanisms, or a lot of them, are transmissible from bacteria to bacteria.

So the bottom line is we cannot dissociate using antibiotics just because it goes into an animal from the fact that bacteria in animals can make its way into human populations. ...

Do we know enough about how much antibiotics is really going into the food chain?

No, the numbers are sporadically reported at best ... We have no systematic method of capturing what antibiotics are being used, how much, where, when, by whom. ...

Do we really know how big the superbug problem is, these resistant organisms that we've been talking about? Do we know how big that problem is in this country?

If you ask me how many KPC, Klebsiella [pneumoniae carbapenemase] infections, how many Acinetobacter, I do not know the answer. How many of them are resistant to this drug or that drug or all drugs? I do not know the answer. There is no data collection that is systematic at a national level that would allow any of us to know the answer to that question.

... Do we understand how they spread?

Different bacteria spread by different means, so things like MRSA, methicillin-resistant Staphylococcus aureus, that lives on our skin, and when we touch stuff and someone else touches it, they can pick it up. Or they can pick it up from our skin.

Other bacteria are environmental bacteria. Some of the Gram negatives, they like soil; they like water; they like living on the walls and on the floors. So different bacteria like different environments and are spread by different ways.

Do we know how many people are dying from these antibiotic-resistant infections?

Not with any certainty. We can make guesstimates from limited data, but we do not have any certainty about those numbers.

You said the government doesn't have a coordinated response, but I'd like to know who should be in charge of this.

I don't know the answer to who should be in charge. We could throw out names. We could throw out [the idea that] the Department of Health and Human Services should appoint someone. But really, part of what government should be doing is determining internally who should be in charge of this.

Is anybody in charge of it?

I do not believe you could name any single person or even a group of two or three people that are in charge of this.

.. Is this a recent problem, or has this been one for quite a while?

The lack of concerted or focused response to antibiotic resistance goes back decades. I mean, it's certainly not a recent problem. I think that in many ways the Obama administration has taken some important steps forward.

They have helped us move toward a public-private partnership model for development. They have tried to coordinate with the Transatlantic Taskforce [on Antimicrobial Resistance (TATFAR)], and they have helped support the passage of the GAIN [Generating Antibiotic Incentives Now] Act, which started the ball rolling to changing the economic model for development.

So it is not the administration's fault. It is not Congress's fault. It is not the Department of Health and Human Services' fault. It's not industry's fault. It's not our fault. It's everyone's fault. It is a collective failure to respond to the problem.

What brings about such a huge failure?

I think that we're spoiled by the success of the early antibiotics, and we came to believe that we would always have them. We just expected that they would be there to cure our diseases, so there was never a need for there to be a concerted, focused, public health policy around this issue.

It seems that you're describing a problem that's a little bit like climate change, too, in that there is a very slow-moving, dangerous threat, but people don't seem to be taking it as urgent.

I think that there are a lot of parallels between antibiotic resistance and climate change. In fact, it was the climate change experience that inspired me to write Rising Plague to try to inform the public about the problem. ... But the one difference is I think that most people, when you tell them, "Hey, you know, we have a problem with superbugs," there is not very much skepticism about it. The public, when you talk to them about superbugs, they understand why it's bad to have superbugs. To try to then come up with a coordinated policy to address the problem is a whole different ballgame.

But the science is settled.

In many ways the science is settled. There are residual questions here and there: What antibiotics should we develop next? What's the best infection-prevention technology? But in many ways the science is settled, and the fact that we have a problem is not in doubt. Nor does Congress doubt that we have a problem. We had bipartisan support to pass GAIN.

Is this really a problem that companies can't make money on antibiotics, or that they just can't make enough money on antibiotics?

The London School of Economics released a report in 2011 that calculated that at discovery, a new systemic antibiotic had what they call a net present value of minus $50 million.

What that means is when you look at the amount of money you'd have to pour into developing the drug and the amount of money you would expect to see returned 20 or 25 years down the line, it's a negative number.

It's a losing proposition.

It's a losing proposition. When you calculate the net present value for an arthritis drug, it's a billion dollars in the green. So you do the math. Even if the London School of Economics was pessimistic and you could make $50 million net, would you rather make the $50 million or the billion?

So the economics are just loaded against antibiotic development.

The science is loaded against it, the economics are loaded against it, and the regulatory is loaded against it. It's a triple threat.