A Conversation With Dame Sally Davies

Friday, September 23, 2016
Morris MacMatzen/Reuters
Sally Davies

Chief Medical Officer for England, United Kingdom of Great Britain and Northern Ireland

Dame Sally Davies, chief medical officer for England, joins CFR’s William Karesh to discuss the challenges of responding to antimicrobial resistance (AMR) and the need for a global action plan following the high-level meeting on antimicrobial resistance at the United Nations General Assembly.

KARESH: Welcome to today’s Council on Foreign Relations meeting with Dame Sally Davies—we’re honored to have you here—on “The Fight Against Antimicrobial Resistance.”

Just as a little reminder, please turn your cellphones off and not just on silent because we’re using wireless mics and we’re recording. The other little reminder is the meeting is on record, so there will be attributes, and we’ll be recording the session as well as your questions.

So we’re going to start off. Dame Sally Davies is the chief medical officer for the United Kingdom, based in London. She has a(n) amazing, distinguished history. And interestingly enough, has only recently come under government service, but prior to that has practiced medicine. She was a professor with the London School of Medicine—or Hygiene. And maybe 10, 12 years ago you joined public service, rose, and became very prominent as the leader of the research and development side of things, our equivalent here of the National Institute of Health Research, and was awarded and named a dame during that work, even before you became chief medical officer—and so this is a more recent thing, in the past four or five years—and has been a global leader in this issue about antimicrobial resistance. Hence, why she was invited to speak with you members and the Council.

So it’s a growing issue, which we’re going to discuss a little more about today, but it’s been wonderful to see the leadership of the U.K. and Dame Sally on this issue, and really pushing it, and leading up to this week’s events at the United Nations. So we’ll talk about—so, welcome.

DAVIES: Thank you. Lovely to be here.

KARESH: So, for some of you that are involved with medicine and antimicrobial resistance in particular you might know, but for others, since long before there were human beings and long before there were animals, and in a time when we only had plants and fungi and bacteria living on this planet, organisms were producing chemicals to protect themselves from infection. So there’s always been a long history, and you can go out into the remotest places on Earth and you will find antimicrobial resistance in organisms, in plants and in animals, because it’s a(n) evolutionary process to fight off infection. But, in the last few decades, this has turned into somewhat of a disastrous situation.

So I thought I’d start with you and say: What has changed?

DAVIES: Well, it was predicted in 1945 by Alexander Fleming, when he accepted his Nobel Prize for penicillin. And he said resistance will occur, and it will cause deaths. So what we’re talking about is infectious organisms. And the urgent one at the moment is bacteria and all the families of bacteria—but it could be, as you said, fungi, viruses, whatever we’re talking about—where they have across the globe developed resistance so that, when they infect people and they’re resistant organisms, you have a drug-resistant infection.

So, worldwide, at least 700,000 people die a year. Let’s make it real for the United States: the equivalent of a Boeing 747 dropping out of the sky every week in the United States, 25,000 deaths. The same in Europe. Take India: 60,000 newborn babies dying of infections that are resistant to drugs every year.

It is actually Darwin’s natural selection. You get a bug doing very nicely, thank you. You put it in somewhere with an antibiotic—maybe the human, but it may be the earth, it may be in water or it may be in animals. And then, because spontaneously a mutation happens that gives it a survival advantage in the presence of that antibiotic, they then proliferate.

It’s interesting because, of course, bacteria multiply every 30 minutes. So, from one bacteria, in 10 hours you can get a billion bacteria. Fascinating, because they don’t just pass it downwards; they can actually pass resistant genes to their neighbors, to their brothers and sisters, their cousins, and then they will pass it down. So it is actually quite a scary scenario.

And it’s made all the more scary because when I was young and practicing medicine, and you were treating people too, what happened was, huh, a resistant organism; OK, open the cupboard, get out a new antibiotic. But unfortunately, we have run out of new antibiotic. There’s no new class of antibiotics come into use—clinical use—since 1987. There have been various improvements and drugs coming, but classes of real novelty, not yet. There are some in the pipeline. But we have across the world disinvested in research in this area, and we don’t have a good pipeline.

KARESH: So I want to get into this pipeline issue: Why can’t we just produce a better antibiotic next week? Why can’t we do it quickly? But before that, I want to start as, is this just—why aren’t doctors fixing this problem? This is a human health issue. And I’m kind of setting you up, because I’ve heard you speak, and you understand this concept of One Health—that we can’t separate the health of people from the planet, and separate human health from animal health, and it’s all interconnected. So I thought—you seem to speak out on that, and I thought you might want to share some thoughts with this group. It’s not just a human issue.

DAVIES: It isn’t. It’s the humans that suffer and die, but we misuse antibiotics everywhere.

So over 50 percent of antibiotics worldwide are used in animals and agriculture, including fish farming, actually. In the States, it’s about 80 percent of your antibiotics are used in animal production. They’re used for growth promotion and in well animals. So they’re actually substituting for good hygiene and sanitation. And as a result, infections—drug-resistant infections are more prevalent in the States. My working assumption is that your waste disposal is effective, your sewage is effective. But if you go to big farms in China, where they also use antibiotics for growth promotion, the runoff from those farms is full of antibiotics because when animals, including the human animal, eats antibiotic and/or take them, we excrete 70 to 80 percent of the antibiotics as they are. The rest is residues. So it goes straight into the environment unless you’ve got good waste management.

So there’s a river in India which has levels of ciprofloxacin, which is a very important antibiotic, of the level that we would like to see in the blood. It is just quite shocking how runoff from intensive farming, high-use hospitals—and the Chinese and Indians have the highest use in their hospitals—from factories making pharmaceuticals or their precursor models are running into our environment and poisoning our environment. And then what you get, we see off the south coast of England, where people do surfing and watersports, is e-coli, a type of bacteria, in the water and increasingly high levels with resistance in them. So if you swallow it, it could give you diarrhea and give you—and it would be a resistant bug that you got.

So One Health is about animals, humans, fish, the environment, and it embraces all our activities and everyone.

KARESH: And clearly, with global trade, these products are moving around the world. But even beyond that, we’ve seen, as you started to refer to, the bacteria themselves can transfer these genes. So we see it spreading in wildlife, potentially rainfall. It’s found in the Antarctic now. Is that true?

DAVIES: Mmm hmm, and the Amazon.

KARESH: And the Amazon. So the remotest places on Earth, not touched.

So let’s get back to some of this other kind of concept of One Health, of prevention versus treatment. So we have a challenge in developing new antibiotics, and maybe you could explain a little of what that is about. And also, what could we be doing better for prevention so we don’t end up in this situation so gravely?

DAVIES: Well, the biggest preventions are actually relatively simple. They’re good sanitation and hygiene for humans, animals, agriculture, the food chain. And it sounds to us in this world so terribly easy, but that means clean water, sewage, lavatories, sewage, sewage management. So I guess, like me, you were thrilled when Prime Minister Modi announced he was going to build 60,000 toilets in India. But then, when people went to look how it was going, they found that many of the ones that had been built were not being used for the purpose they were built for.

I just realized you’re still eating lunch; sorry about this. (Laughter.)

Built—for the purpose they were built for, but actually the men—it would be the men, I’d say—(laughter)—are using them for storage purposes, and the women are still having to go into the fields. There’s a side of that as well; it’s not just about the poor sanitation. It is also tragic, because women are at high risk of being attacked and sexually molested if they go out into the fields because it’s a very easy time to catch them with their pants down. So it is an issue of sanitation/hygiene throughout the world.

But we also have to use our antibiotics and conserve them, and it’s called stewardship. Use them when they’re needed, not for growth promotion. Use the right antibiotics. So, in hospitals, it is quite common in our country—I don’t know whether it is in yours—a patient is sick, probably needs an antibiotic, so you take the blood cultures and you put them on the antibiotics in hospital, then you put them on broad spread—broad ones. But the important thing then is when the culture results come through, if nothing grew, you should stop them; if something grew and it’s right, OK, go on; but if something grew and they’re the wrong antibiotics, change them. And all too frequently, doctors are sloppy and just leave them on the ones they’re on. So we really need to make sure that we have good guidelines, but also that we follow them. And I think both of these examples I’ve used show you that this is a behavioral issue.

Take sore throats. Many people go to the general practitioner, the community physician with a sore throat. We’ve got research that shows if they get a tablet they feel validated they’re truly sick. Probably 10 percent need antibiotics. But in Britain, about 60 percent get antibiotic. And it’s a really tough one for the GPs. They have my sympathy—you know, a mother demanding an antibiotic for their child so they can go to school, no real diagnostic there to be certain. It is a very difficult one. We have managed to reduce prescribing by some behavioral techniques, but it is worrying that antibiotics are being prescribed when they’re not needed, just as it’s worrying that across the world more people at the moment are dying because they don’t get antibiotics when they need them than are dying because of resistance. It’s just that it’s set to rise, and now we’ve got to take action or our children and grandchildren will have a dreadful life.

The work by the independent review that our prime minister commissioned that you mentioned on AMR, led by Lord O’Neill, who used to be Goldman Sachs’ asset management senior economist, models that if we don’t take effective action, by 2050 there will be 10 million deaths every year, and that it will cost up to 100 trillion pounds to the economy—be the equivalent of losing the U.K.’s GDP every year to the economy. So we have a chance to get on top of this, but it needs bold and strong action across this One Health spectrum, including animals and agriculture. And people find it difficult to take bold action.

KARESH: Yes, I imagine so. And this week one bold action was taken, but I’d like to discuss the meaning of that and the significance. But for any of you that are not familiar, this week there was a high-level meeting at the United Nations with the general session here or General Assembly here on this issue with antimicrobial resistance. It’s only the third time in history of the United Nations that a health issue has been brought up—once on non-communicable diseases, once on HIV/AIDS, and now this week on antimicrobial resistance. So it shows how important the U.N. is taking it.

Some might say, oh, it’s too late—too little, too late—but I wouldn’t agree with that, because I think, you know, that recognition that we need to come together is essential. And you had a lot to do in the U.K. with driving this issue forward. So if you want to share some thoughts on what the resolution means and where we can go from here.

DAVIES: Thank you. It’s a good thing I didn’t know that this wasn’t the normal way of doing things two years ago when I prodded the British government said, this is what we’re going to do: we’re going to the U.N. high-level assembly. It was only recently I discovered it would be the third issue done here.

And the reason we, with the support of many countries; working with WHO; the Organization for Animal Health, OIE; the Food and Agriculture Organization, through which we’d put resolutions getting countries to take action, but also to support coming here; it’s because this is what you could call a wicked problem. And the impact may be on human health—well, is on human health—but human health people, doctors, can’t sort it out. We can reduce antibiotic use, but it’s not in our hands to sort the innovations needed, which is around new antibiotics and better diagnostics and better ways of surveillance. It’s not in our hands to impact the veterinary use or the fish-farm use. It’s not in our hands to do more than to comment and advise on the environmental contamination.

So we can raise it, but to resolve this needs cross-government approaches. And in my experience, you only get that to happen when you get the finance ministers involved. So that was why our government commissioned Lord O’Neill to do an AMR review looking at it from the economic perspective. And he then took that to the G-20, the Group of 20, and their finance ministers have been very exercised by his report, and have agreed through the heads of state meeting in Guangzhou (sic; Hangzhou) September 4th-5th that they will commission some work about the innovation issues and market failure. So I think that that’s getting traction.

I should add, as you know, that the World Bank produced a report that we part funded that I’ve been chivvying them to do for two years looking at the economics as well. And having started by saying, oh, it’s not as bad as Lord Jim says, actually their modeling suggested it’ll be even worse economically than Lord Jim says, and it will push people in lower-income countries into poverty if we don’t take action. So I think that’s very compelling, that we’ve got two reports—one from someone totally independent, and then the World Bank, who were skeptical, and then come up and say, hey, guys, we really do need to sort this.

So the power of the U.N. General Assembly high-level meeting is the focus, the attention—there were 12 side events on AMR; I’ve been running between them all—and then the resolution, which commits the secretary-general, with the WHO, to set up a convening committee to kind of ensure there’s follow-up and there’s work done so that the secretary-general can report back in two years’ time to the U.N. General Assembly. So it’s not a hey, guys, there’s a problem; it’s a hey, guys, there’s a problem, we’re going to set up a committee that needs to push people to do something, and we want to hear much more detail about where we are and what needs doing in two years’ time. Quite a powerful resolution.

KARESH: So, for some of you, there’s an organization called the World Organization for Animal Health, which is U.N.-like. It started a little before the U.N. And their member countries have all promised—they passed a resolution last year that every country would report antimicrobial use in animals on an annual basis so we could get a handle, really the first time we actually know what’s being used. In the U.N. resolution or with the next steps, will some of that be happening across disciplines or across sectors?

DAVIES: It should be, because in fact there’s a global action plan, written by WHO with input from FAO and OIE—accepted first of all by the 190, however many states it is, member states of the WHO, but then it went through the FAO and the OIE. So all three have agreed to work together, One Health, and agreed to collect the data, and to support national action plans. So in two years’ time, when we come back, every country is supposed to have a national action plan.

Of course, we all know a national action plan could sit on a bookshelf and not lead to action. So we do, then, need—also need to collect the data to see what’s happening and how it’s working.

KARESH: OK. What can we do as members while those action plans are moving along and going on bookshelves?

DAVIES: Ah, well, I always start by saying we could learn to wash our hands properly, you know. There’s a study from a motorway service station showing that 40 percent of women didn’t wash their hands properly, but 60 percent of men didn’t. So important that we teach people to do that.

And hygiene—food hygiene, all hygiene, particularly in institutions. There is, in the States—I don’t know whether it’s an act or what it is, but essentially the FDA has asked that voluntarily antibiotics should be taken out of growth promotion by the new year, and I think that would be a very good move.

But I think we have a role as consumers. So, the first evening we were here, we went down to find Shake Shack. I don’t know whether the food’s any good, but it says on it chicken’s antibiotic-free. And that means that—I understand that that means they haven’t used them in the raising of those chickens. There is a difference, of course, between antibiotic-free—they were not used to raise them—and antibiotic-residue-free: well, they may have had some in the past, but they’ve been around for a few days since they had them, so there’s no active antibiotic in their body. But there could, of course, be bacteria that are resistant on their bodies. So I think the consumer pressure is beginning to take effect in the States. And the more you can do that, the better, because I can tell you, Britain follows and then Europe follows. And if we could get all of that to work, then it would begin to roll across the nations.

But also, when you next get a sore throat, if the doctor says you don’t really need an antibiotic, take their word for it. Don’t demand it—or buy it over the internet, tut-tut. (Laughter, laughs.)

KARESH: Well, I’m not part of the New York City Public Health Department, but we kind of—we tend to watch and say, well, when New York City Public Health does something, the rest of the country tends to follow. Much like we used to look at California with emissions on cars, and what California does the industry and consumers tend to follow. So I would push us for a leadership role. I heard a little tidbit last week that New York City is the second-largest purchaser of poultry in the United States. So the number one purchaser of poultry in the United States is the U.S. Defense Department—(laughter)—and the second is New York City, the city government of New York, because we use so much to feed. And that’s—and they’re considering, like we have in the other public health arenas, about getting—purchasing antibiotic-free chicken and helping to stimulate that market so farmers can actually make more money by providing that product. So we have to find some mechanisms that don’t penalize producers, don’t penalize companies, but actually stimulate a new kind of industry direction.

DAVIES: So the Danes did—have done the experiment, both in chickens and pork. They don’t grow beef. And what happened to output was in the first year it dropped off, but by year two the output was back at the same level, and then it went on up. So—

KARESH: Without using antibiotics.

DAVIES: Without using antibiotics. So there is an upfront cost around the hygiene and the sanitation, but you get back pretty quickly, if you lose it at all, to the same output. And what I read and learn is that if you are in a developed country, the added protein from growth-promoting antibiotics is minimal. It makes a much bigger difference when you’re in the developing world. So, come on, America! Join Europe. We have led the way on this one. (Laughter.)

KARESH: (Laughs.) That’s great. I think—thank you for this. We’re going to open this up for questions. And once again, remember this is being recorded and the comments are on record. If you have a question for Dame Sally, please also—I think we’ll have—use the microphone so we can capture it. Please identify yourself and the institution with which you work. If you would, please start here and we’ll come around the table this way.

Q: Bettye Musham, private investment (company ?).

What PR is being done so that people are aware of this? And do you work with the pig-growing unions and the chicken farmers? I mean, if you get to the core, isn’t that better than dealing with the sewage?

DAVIES: Absolutely. Everyone says we need more communication, we need more engagement, we need more education. And then you get back to it has to be tailored to the audience, to the culture, and who’s going to pay for it. It’s proving quite difficult. We have a number of efforts in Britain, and when we do put communications in place they generally pay off. But it’s a costly business. But losing lives is rather expensive, too, I believe.


DAVIES: Cheap for the health system.

KARESH: I would add that it’s—because of this number we keep speaking about, 80 percent of antibiotics used on the planet are given to animals for food, so it does sound like that’s the biggest problem for antimicrobial resistance. But, in fact, most of the human antimicrobial resistance, a lot of it—probably the majority—is linked to the way we treat people.


KARESH: Just to be fair and balanced in this conversation. So the overuse or the misuse—I know when I go to my physician, who I adore—and this is on record; maybe I shouldn’t have said—friends of mine, when they go to their physicians—(laughter)—you know, I tend to get, like, the most expensive, advanced antibiotic, you know, available if I’m coughing instead of ampicillin or amoxicillin. So there’s a little of that—

DAVIES: Or a pat on the back and, dear, dear, you’ve got a virus.

KARESH: Yes, but take this antibiotic anyway. (Laughter.) So I—you know, so—

DAVIES: (Laughs.) Not if I was your doctor. But then you wouldn’t adore me. (Laughter.)

KARESH: So I think it spans across. I mean, it’s turning into an all-of-society issue.

DAVIES: It is.

KARESH: Yes. But your point’s well-taken.

Yes, sir. And then we’ll—

Q: Tom Mahoney from Tangent Capital Partners.

As a former synthetic organic chemist who did antibiotic research when it was not oxymoronic—

KARESH: (Laughs.)

Q: —I’m interested in—before things like beta-lactamases got invented by the bugs, right, to deactivate the penicillins and cephalosporins and other, older weapons in our armamentarium, I’m interested, in addition to the spread of traditional—the overuse of traditional antibiotics, things like, you know, antibacterials—the surface-acting antibacterials, the triclosans, the quaternary ammonium compounds like benzalkonium chloride and things like that—there seems to be some suggestion that sometimes these things can have an intracellular action as well, which can lead to multi-drug resistance and other terrible phenomena. What are your thoughts? And what has been the experience in your work in the U.K. around that particular issue and its interaction with the overuse of antibiotics per se?

DAVIES: Well, I think you probably know more about this than me. So I’m aware of those reports. I’m quite concerned, because we have had a growth, at least in Britain, in a belief of almost obsessional cleanliness. So, I want cleanliness, but there is, as you know, evidence of increasing allergy, which may link to some of this, and now the discussion about what are the antibacterials doing, used in every kitchen on everything.

You and I know that good old soap and water is very effective. And we probably need to go back much more to that to try and protect them as well, except in certain situations of course. I think in an abattoir’s food chain and everything, where there’s a lot of food, you wouldn’t want to change. But at home, all of this has made sure we stick to soap and water.

KARESH: Yes, sir.

Q: Alex Skora, Estron Chemical.

You had cited the Danish example earlier. Are there any other countries in the world that have tried to tackle this legislatively? Because up to now it seems like all the initiatives have been voluntary guidelines that have been put out on an ad hoc or piecemeal basis. And could you speak a little bit to that?

DAVIES: Yes, the whole of Europe.

Q: Whole of Europe.

DAVIES: In 2006 the European Union said no antibiotics for growth promotion, and it’s been very successful. The—I can’t remember the exact date, but more recently the Dutch realized they have quite high levels, and they decided to put in even stricter laws. And they have been able to reduce their use. And we do have a north-south kind of gradient, where the further north in Europe you are, the fewer antibiotics are used in animals and humans.

The other interesting thing about the north is that—it started in Norway, but we do it in Scotland as well—is that, for fish farming, for salmon and trout, instead of using antibiotics in the feed, they use individual vaccination of the animals, three vaccines put into one. Now, I understand they’re now moving to an oral vaccine that you can put into the feed; so, interestingly, dropping that, and therefore the impact on the seawater or the river water runoff. We can do a lot if we really—and, come on, industry is full of wonderful scientists who are very innovative. If we had the regulations, they’d find a way to respond effectively. I have great belief in our scientists.

KARESH: Two questions over here. Please.

Q: Thank you very much for your remarks. Tyler Smith with Earthjustice.

I’m wondering—you’ve mentioned a number of times this issue of the growth-promotion use of antibiotics and how Europe has banned it and the FDA is moving towards a voluntary phaseout.

Going beyond that—and I think you hinted at this with Norway and the Netherlands and elsewhere, and thinking about the prophylactic use of antibiotics in animals, often the same drugs at the same dose for extended durations in feed and water. The Food and Drug Administration here has not really done much of anything to address that use, whereas countries like Denmark and the Netherlands are leading the way.

And if I can ask you to risk controversy, could you comment on what you think the U.S. might be doing differently or what strategies might be pursued here to deal with prophylactic or preventive use of antibiotics on livestock?

DAVIES: So there seem to be—but you may know more than me, so correct me if I’m wrong—three uses of antibiotics, three in animals. There’s growth promotion; they’re well. There’s treating sick animals. No, there are four uses; I’ve got that—there’s treating sick animals, which we all agree needs to happen. If you have a sick animal in a flock or a herd, there is an argument for treating the rest to contain it and to get on with it. And that, I think, is called prophylaxis. But then—or is it metaphylaxis? I—

Q: (Off mic.)

DAVIES: That’s metaphylaxis. I can buy that. Then what a number of places do is they say, well, it’s not growth promotion, but the whole flock could be or herd could be at risk, so we’ll just give healthy animals antibiotics. And that’s prophylaxis. And that would seem to me to be wrong.

So how do we move to make sure that ill animals are treated, that flocks are protected when there is an ill one, but we don’t overuse them? I think every country will find different ways to do that. And there will be always people who go against the grain. But I do think regulation and inspection plays a role in that. And the veterinary professionals play a key role.

But increasingly, antibiotics are available over the Web. So even in Britain, where they’re not allowed to be used, not prescribed by a doctor or a vet, you can log in and find—I’ve forgotten the numbers now; I think it was 132 companies that would ship antibiotics directly in brown packages into the U.K. So because of the Web, people can bypass it.

So we are going to have to have not only regulations, but inspections. And ideally—I would have loved it, but I think it’ll take a while—close down Internet sales of antibiotics, because some of those you can buy off the Internet are on the WHO’s critically important list that should not be taken, used in the animal sector at all. That’s supposed to be reserved for humans only. So it’s really quite a scary picture.

Q: (Off mic)—Council member, and I have two very different questions.

One is around R&D incentives, both for diseases of poverty, like DRTB, and then, you know, more like what we see in hospital infections in the U.S.

And the second question, totally different, is, as you know, pneumonia is the leading killer of children, and in most places people don’t have access to vaccines, although that’s coming. And so there’s a big push in the global health community for widespread community-based distribution of antibiotics. Can you comment a little bit on your thought on that and how it relates to the—

DAVIES: So let’s go in reverse order. So there is a study that shows if you have widespread access for children aged under five to antibiotics, you save a lot of lives. I did know the number this morning. I’ve forgotten the number. And I’m not against that. What we need steadily to move to is stronger health systems so that they’re actually getting—and rapid diagnostics, so they’re properly diagnosed and they get the right antibiotic, and the ones that don’t need them don’t get them. But we know more people die of lack of access than resistance at the moment. So if that is an interim step to a much better whole system, then we have to take those risks. We can’t let those children die.

We have a really difficult market at the moment for research. Academia has disinvested. Pharma companies have generally disinvested in research for antibiotics; partly a market failure that we don’t pay much for antibiotics. You probably know all this, but I’ll say it anyway. We don’t pay very much in comparison with cancer drugs. Meanwhile, if you have a diabetes or a hypertension drug, the profit might be minuscule, but you get that profit day in and day out for the rest of the people’s lives, whereas antibiotics you take for a short time. So there’s no market pull.

I think it was compounded by people going through a couple of kind of fashionable phases—I don’t know what you think—but that, oh, we’ll find new drugs through genomics and genomic redoing, and then, oh, it’s all small molecules. Actually, it probably was the other way around or simultaneous. And we can design them on a computer where actually the successful antibiotics have all come from—they’re all complex molecules coming from natural products and things. And you can’t design those on a computer and you can’t—you can tinker with them on a computer and improve them and make them safer or more absorbable, but also with genomics.

So I think that the fact that we went through these fashions and they didn’t work for this so there were no drugs coming through made it less easy to invest there. We do need to invest. Lord O’Neill’s review talks about this and suggests a number of mechanisms. We should up our funding in the basic sciences, a lot in academia—NIH needs to play its role, and the equivalent in Europe—but some also in pharma and biotech.

But then who develops drugs? It has to be the private sector. So do we move to a new market-entry system where you delink the R&D costs from volume? And that’s what he recommends. And I can see that that is a good move. But then you’ve got to move into kind of funding prizes for getting to various stages in the development and have in place really good stewardship so that the volume is contained. And it’s quite complex.

So he’s made a recommendation. A number of other people have come up with other recommendations, but they all involve that kind of delinking. And the G-20 has remitted it to OECD, the World Bank, the WHO, et al, to have a think and come back with some suggestions to them in a year’s time; so a lot of work about (to take off ?). And there must be a way of doing this.

KARESH: Yes, sir, and then—

Q: I’m Brad Connor. I’m with the Weill Cornell Medical College and the New York Center for Travel and Tropical Medicine.

So as far as physician responsibility—I’m a physician—it’s a little daunting now to hear that 80 percent of the problem is the animal—

DAVIES: No, the consumption is animal.

KARESH: Consumption is not the problem.

DAVIES: The problem is in the—the human use is the biggest driver.

KARESH: (Laughs.)

Q: All right. So as a result, you know—

KARESH: Thank you.

Q: —the physician community needs to be engaged in a much more aggressive way. We had a consensus conference in April of the International Society of Travel Medicine with the CDC to discuss antibiotic use in travel. And studies have shown that just traveling without using antibiotics is associated with the acquisition of resistance. (Finnish ?) studies show that 25 percent of travelers to India, whether they took antibiotics or not, came back with resistant organisms. If you took an antibiotic, 80 percent came back with—(off mic)—resistant.

So at the consensus conference, we rewrote the guidelines for—(off mic)—saying, in mild to moderate cases, we should go back to compounds like—(off mic)—agents, perhaps the use of prebiotics that feed the healthy—(off mic)—bacteria as a protection. So we need to look at things in a different way.

Another comment I’d like to make is vaccination. So, by using vaccines to stimulate your body’s own immunity, you get out of the whole antibiotic realm completely. And a lot of the vaccine-preventable diseases are wonderful (examples ?) the fact that we don’t have to use antibiotics in certain diseases. So I think that’s part of the—of the message also, is development of vaccines, which are sort of the body’s own way of fighting—(off mic). So some comments. I don’t know—(off mic).

DAVIES: Well, I absolutely agree. And I was at the Gates Foundation last week, and they were saying they’re going to evaluate the impact of pneumococcal vaccine in Africa, because it’s clear that in the developed world it has reduced antibiotic use. We’re seeing a dropping of some resistance. And it has made a big impact. We’re seeing fewer infections, less antibiotic use, and less resistance in that arena of community chest infections. So it’s probably happening everywhere.

We need more vaccines. And interestingly, I asked OIE, oh, over a year ago now, to have a look what were the vaccines that needed making for animal husbandry. And they came up with for pigs it’s this and for cows it’s that, and everything. So there is a list that industry can look at and think whether they want to get into it. But we’re going to need cheap vaccines. That doesn’t mean it can’t be done. It’s just it may be novel technologies or different ways of doing it.

Q: Thank you.

KARESH: Two—I think two people at your table please.

Q: Drew Ladner, Pascal Metrics. Thanks very much for your remarks.

I have a question about the health-care-delivery side of issue and how they might be used to marshal support to solve the overall problem. As you probably are aware, Dr. Marty Makary, recently in the BMJ, wrote a piece on medical error being the third-leading cause of death in the U.S., building on other studies like the John James study, David Classen study, others that have gone before, that have shown that one out of three patients in U.S. hospitals suffers an adverse event. The cost is up to $63 billion. And this is a pervasive problem that affects man and woman in the street.

So the question is, if the overall safety problem is measured in 10 747s per week, what is your view on the degree to which the stewardship issue can be wrapped in a broader safety issue and really, through the clinical value of reducing harm, the finance piece, which is huge—you know, health systems here are showing hundreds of basis points of cost on the adverse-event side—but also wrapping in safety so that the man and woman in the street can access this issue a little bit more easily than the technical discussion that obviously some of the more expert folks in the room clearly have command of.

What’s your thought of tying it to safety?

DAVIES: I think it is a part of the safety agenda when you’re talking about hospitals. Indeed, my secretary for health held an international conference on patient safety, and I spoke on just exactly this, because it is infection prevention and control so you don’t get MRSA and C Diff. It’s about using antibiotics safely, and actually some of the more expensive, more modern antibiotics, as well as Colistin, the very old one that’s coming back, had nasty side effects, adverse events. So you’re back into safety from there.

So I think in hospitals it’s a core part of that agenda. It’s just that it’s more complex than just hospitals. It’s overuse in the community and it’s this One Health issues of animals and environment. And even the production of them for use in hospitals can have runoff problems and poison the environment. But I’m with you.

But it’s a faceless problem. How many of you know—knowingly know someone—you all know someone who’s got antibiotic resistance or had it—but how many of you know about it happening to a friend or a relative? Oh, some of you do. That’s interesting, because generally it’s pretty faceless. And isn’t it tragedy that a child can be cured of leukemia and then die of an infection because the antibiotics didn’t work? And it’s that sort of thing we’re talking about. But somehow everyone thinks they died of the cancer, even though they were cured of it or in remission.

KARESH: I think there was a question—please go ahead. And then was there somebody at the last—the back table also?

Q: Sir, my name is—my name is Clive Meanwell. I should declare that we were one of the recipients of a BADA (ph) grant this week, $132 million for R&D. Thank you. Your personal drive over the last years is a very direct reason why that happened. Thank you.

But I want to talk about de-linking. I was involved in developing drugs when HIV started up. We didn’t talk about de-link. We talked about innovation, drive. We discussed it very briefly at that time, and I think the conclusion was that the drive for technological innovation would ultimately win. Why wouldn’t it win here? Why wouldn’t we restrict the breadth of antibiotic use? Why would we pay $100,000 for a cancer drug, but no more than 8(,000 dollars), $9,000 for an antibiotic that could save the same 45-year-old woman with two children? That’s something I don’t really understand. When you’ve been in those big meetings, what is avoiding that subject? Is it EpiPen problem? Is it just the politics of price? Or is it something else? We really think de-linkage is a better way forward.

DAVIES: It’s interesting, isn’t it, which is why it’s not for me to decide how we should sort this. So I’d make a few comments.

You can drive innovation lots of ways, but at the moment it isn’t working. So is it we raise the price? But if we raise the price, we restrict their availability. And then there will be many deaths when we do have an effective drug. And you might say to me, well, that happens with cancer, and that’s acceptable there. But actually, many of these cancer drugs that are not being bought are not cost-effective.

To put antibiotics into the same area when they are a common good, we would argue, is, I think, a very difficult moral dilemma. I mean, the particular problem with antibiotics is—I’m told economists call it—you probably know better than me—the tragedy of the commons; that if it’s there and I’ve got an infection, I want it, and I discount the impact on the future generations or other people at the time.

And that’s quite different from cancer, because if it’s there and I want it, I ought to get it and get better, or I don’t get it, but it hasn’t impacted on anyone else. And I think that tragedy of the commons alters both the financial debate, because it becomes a common good that we must all protect and we must try and make available.

So you’d then perhaps counter and say, well, Yusuf Hamied did make retrovirals available, but it took some years and it was a very bumpy path, and there had to be big funds set up to buy them for people and everything. And I think what we’re trying to find, but I don’t—I’m not an economist—is a way to protect what we’ve got but make sure there’s adequate access and pull through more.

Complex, isn’t it?

KARESH: Yes. More questions? Yes, sir. Could you introduce yourself, too?

Q: David Bard, American Securities.

On that point—and this may be down a path you don’t want to go down—but usually when you have that kind of tragedy of the commons, also referred to as an externality, the solution is to either create property rights or to take that cost and force those who otherwise don’t incur it to incur it, which actually involves raising prices often. Is there any creative economic thinking anyone’s done about how to apply some of that thinking such that that externality, that tragedy of the commons could be alleviated?

DAVIES: Well, Jim O’Neill’s suggestion was a model he calls pay or play, where the companies in the field of health—well, medication, shall I say—either fund research in this area or they pay a levy into a fund, so they do pay, for others to do it. So you get a choice of pay or play. And it even worked out what percentage it would be, and it would be very small. So people are beginning to look at exactly that sort of model. But it’s outside my competence.

KARESH: Well, are there other examples? I mean, this is—we’re describing as this dilemma between individual health care and public health, the practice of individual medicine, the conflict with public health. And antibiotics certainly fall in this tragedy of the commons dilemma there.

DAVIES: Are there others in health? I don’t know. I mean, clearly, climate change is the classic tragedy of the commons, isn’t it? So you have to look for things where there are common good that we discount our own use of them because we think we’re more important today than others will be tomorrow. Maybe others can help us through that one.

KARESH: And there’s—for the people that are producing these products, of course, prevention doesn’t help them make money. So there’s always the traditional shift in medicine too, that, you know, prevention is always better, as Ben Franklin said. But the money is in the treatments. But I think, you know, we have to recognize there’s not a lot of money on the prevention side.

DAVIES: There may not be.

KARESH: Or profits to be made, yes, to society.

DAVIES: But I think that in the end this will become a corporate social responsibility issue, and that companies will want—I mean, if there’s another way we can put pressure as consumers. We can do it through shareholders. You know, why are we investing in you to make anti-cancer drugs and everything, and you’re not doing your social responsibility?

But one of my answers to the chief executives of some of our big pharma companies is so when this gets bad and I get cancer, and my physician says to me, well, I can give you an anti-cancer drug which will probably cure you, but you’re sure to get an infection, and I don’t think I’ve got an antibiotic for it, what am I going to do? So I’ll have that expensive anti-cancer drug, which will be unpleasant, won’t it, anyway, and then I’ll probably die of an infection or do my bucket list.

You know, we will get to a point where we will not want to buy the expensive anti-cancer drugs and things because of the immune suppression and the fact that they will get infections that we can’t treat. So it is in their self-interest, but they’re only just waking up to that.

KARESH: Or the hip-replacement surgery. We’re sorry, we won’t be able to do that. We could do the surgery, but you will die from an infection later.

DAVIES: Yeah. One in three will get an infection unless they’re really clean and slick.

KARESH: So I think we have time, maybe, for one more question. We’re all happy, satisfied. Oh. Yes, sir.

Q: (Off mic)—your point about prevention and making money. First of all, tragedy of the commons, pastoralists and capture fisheries. They’re too other tragedies of the commons.

DAVIES: Thank you.

Q: But if one thinks about diagnostics, OK, and a preventive role diagnostics can play, just simply bacterial versus viral, if you create a massive market for that, either through legislation or—(inaudible)—I mean, there’s huge money to be made in that. So, Dame Sally, I mean, what sort of prospects are you seeing in terms of timeframes for rapid point-of-care diagnostics that might help provide GPs with the ammunition to say you’re not getting an antibiotic and you really don’t need an antibiotic, and I have the test that proves you don’t need an antibiotic.

DAVIES: Thank you. I should have brought that in and didn’t. And you’re right. We could, at a stroke, change how we use antibiotics if we had good rapid diagnostics. It’s quite difficult how you put in the force, the regulation. And Jim O’Neill, as you know, recommended that by 2020 you should not be able to prescribe an antibiotic in the community without a rapid diagnostic. And he’s pretty pissed off with me that I haven’t found a way to do that. (Laughter.)

What we are doing is asking our National Institute of—NICE to look not just once, but on a regular basis, at what rapid diagnostics there are and the cost effectiveness of those, because it will come to a point where companies will know that at that level it’ll be cost effective. So if it’s sensitive and specific enough, it’ll be worth it. So by then starting to look and do the work, and repeated on a regular basis, we should get there where we’ll be able to introduce that as a quasi-regulation.

That’s the U.K. market. How we’ll spread it—and you probably know we also have in the U.K. the Longitude Prize, which was launched a couple of years ago on the 300th anniversary of the prize to the watchmaker for finding a way of measuring longitude. And it is for a rapid diagnostic to reduce antimicrobial resistance. We’re trying to put—and NIH announced one quite recently—the European Commission has just announced one—we’re trying to put prizes in pull rapid diagnostics. I think we’ll get those. But you’re right, how do we make them used will be the real issue.

KARESH: And I would add, in a similar vein, kind of this bigger thinking about what else could be done. Certainly in the U.S. government, the sector of the government that put up GPS satellites and developed the Worldwide Web, are putting—investing a lot of money into tolerance mechanisms. So we typically think of these infections as a war between us and the microbes, and who’s going to win first, and let’s smack them with something bigger and stronger.

When we have microbes in us more than we have human cells—we have billions—and we tolerate them. And what are the mechanisms for that? So maybe as a patient comes in, we do something to boost their tolerance, which gets rid of this evolutionary process of the bacteria is evolving to fight the drug that’s trying to kill them. You have it. You tolerate it. They reproduce and they go on.

There’s some kind of big ideas, including bedside diagnostics; so a lot of potential and hope for the future.

DAVIES: I have hope.

KARESH: I do too.

So, Dame Sally, thank you so much for spending time with us. (Applause.)

DAVIES: Thank you.


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