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The first patient to be treated with an antibiotic

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was a policeman from Oxford.

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On his day off from work,

4
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he was scratched by a rose thorn
while working in the garden.

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That small scratch became infected.

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Over the next few days, his head was swollen

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with abscesses,

8
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and in fact his eye was so infected

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that they had to take it out,

10
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and by February of 1941,

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this poor man was on the verge of dying.

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He was at Radcliffe Infirmary in Oxford,

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and fortunately for him,

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a small team of doctors

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led by a Dr. Howard Florey

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had managed to synthesize

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a very small amount of penicillin,

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a drug that had been discovered

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12 years before by Alexander Fleming

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but had never actually been used to treat a human,

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and indeed no one even knew if the drug would work,

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if it was full of impurities that would kill the patient,

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but Florey and his team figured

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if they had to use it, they might as well use it

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on someone who was going to die anyway.

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So they gave Albert Alexander,

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this Oxford policeman, the drug,

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and within 24 hours,

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he started getting better.

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His fever went down, his appetite came back.

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Secondly, he was doing much better.

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He was starting to run out of penicillin,

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so what they would do was run with his urine

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across the road to re-synthesize the penicillin

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from his urine and give it back to him,

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and that worked.

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Day four, well on the way to recovery.

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This was a miracle.

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Day five, they ran out of penicillin,

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and the poor man died.

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So that story didn't end that well,

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but fortunately for millions of other people

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like this child who was treated again

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in the early 1940s,

45
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who was again dying of abscesses,

46
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and within just six days, you can see,

47
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recovered thanks to this wonder drug penicillin.

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Millions have lived,

49
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and global health has been transformed.

50
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Now, antibiotics have been used

51
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for patients like this,

52
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but they've also been used rather frivolously

53
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in some instances

54
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for treating someone with just a cold or the flu

55
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which they might not have responded to an antibiotic,

56
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and they've also been used in large quantities

57
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sub-therapeutically, which
means in small concentrations,

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to make chicken and hogs grow faster.

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Just to save a few pennies on the price of meat,

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we've spent a lot of antibiotics on animals,

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not for treatment, not for sick animals,

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but primarily for growth promotion.

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Now, what did that lead us to?

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Basically, the massive use of antibiotics

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around the world

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has imposed such large
selection pressure on bacteria

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that resistance is now a problem,

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because we've now selected for just

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the resistant bacteria.

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And I'm sure you've all read
about this in the newspapers,

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you've seen this in every magazine

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that you come across,

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but I really want you to appreciate

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the significance of this problem.

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This is serious.

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The next slide I'm about to show you

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is of carbapenum resistance in acinetobacter.

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Acinetobacter is a nasty hospital bug,

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and carbapenum is pretty much

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the strongest class of antibiotics

81
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that we can throw at this bug.

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And you can see in 1999,

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this is the pattern of resistance,

84
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mostly under about 10 percent
across the United States.

85
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Now watch what happens when we play the video.

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So I don't know where you live,

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but wherever it is, it certainly is a lot worse now

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than it was in 1999,

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and that is the problem of antibiotic resistance.

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It's a global issue

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affecting both rich and poor countries,

92
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and at the heart of it, you might say, well,

93
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isn't this really just a medical issue?

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If we taught doctors of how
not to use antibiotics as much,

95
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if we taught patients how not to demand antibiotics,

96
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perhaps this really wouldn't be an issue,

97
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and maybe the pharmaceutical companies

98
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should be working harder to develop

99
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more antibiotics.

100
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Now, it turns out that there's something

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fundamental about antibiotics

102
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which make it different from other drugs,

103
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which is that if I misuse antibiotics

104
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or I use antibiotics,

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not only am I affected but others are affected as well,

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in the same as if I choose to drive to work

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or take a plane to go somewhere,

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that the costs I impose on others

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through global climate change go everywhere,

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and I don't necessarily take
these costs into consideration.

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This is what economists might call

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a problem of the commons,

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and the problem of the commons is exactly

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what we face in the case of antibiotics as well;

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that we don't consider,

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and we, including individuals, patients,

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hospitals, entire health systems,

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do not consider the costs that they impose on others

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by the way antibiotics are actually used.

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Now, that's a problem that's similar

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to another area that we all know about,

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which is of fuel use, and energy,

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and of course energy use

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both depletes energy as well as

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leads to local pollution and climate change.

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And typically, in the case of energy,

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there are two ways in which
you can deal with the problem.

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One is, we can make better
use of the oil that we have,

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and that's analogous to making better use

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of existing antibiotics,

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and we can do this in a number of ways

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that we'll talk about in a second,

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but the other option is the "drill, baby, drill" option,

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which in the case of antibiotics

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is to go find new antibiotics.

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Now, these are not separate.

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They're related, because if we invest heavily

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in new oil wells,

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we reduce the incentives for conservation of oil

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in the same way that's going to happen for antibiotics.

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The reverse is also going to happen, which is that

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if we use our antibiotics appropriately,

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we don't necessarily have to make the investments

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in new drug development.

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And if you thought that these two were entirely,

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fully balanced between these two options,

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you might consider the fact that

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this is really a game that we're playing.

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The game is really one of coevolution,

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and coevolution is, in this particular picture,

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between cheetahs and gazelles.

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Cheetahs have evolved to run faster,

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because if they didn't run faster,

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they wouldn't get any lunch.

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Gazelles have evolved to run faster because

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if they don't run faster, they would be lunch.

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Now, this is the game we're
playing against the bacteria,

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except we're not the cheetahs,

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we're the gazelles,

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and the bacteria would,

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just in the course of this little talk,

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would have had kids and grandkids

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and figured out how to be resistant

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just by selection and trial and error,

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trying it over and over again.

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Whereas how do we stay ahead of the bacteria?

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We have drug discovery processes,

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screening molecules,

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we have clinical trials,

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and then, when we think we have a drug,

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then we have the FDA regulatory process.

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And once we go through all of that,

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then we try to stay one step ahead

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of the bacteria.

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Now, this is clearly not a game that can be sustained,

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or one that we can win

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by simply innovating to stay ahead.

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We've got to slow the pace of coevolution down,

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and there are ideas that we can borrow from energy

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that are helpful in thinking about

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how we might want to do this in the case

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of antibiotics as well.

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Now, if you think about how we deal with

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energy pricing, for instance,

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we consider emissions taxes,

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which means we're imposing the costs of pollution

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on people who actually use that energy.

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We might consider doing that for antibiotics as well,

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and perhaps that would make sure that antibiotics

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actually get used appropriately.

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There are clean energy subsidies,

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which are to switch to fuels
which don't pollute as much

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or perhaps don't need fossil fuels.

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Now, the analogy here is perhaps we need

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to move away from using antibiotics,

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and if you think about it,

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what are good substitutes for antibiotics?

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Well, turns out that anything that reduces

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the need for the antibiotic would really work,

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so that could include improving
hospital infection control

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or vaccinating people,

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particularly against the seasonal influenza,

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and the seasonal flu is probably

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the biggest driver of antibiotic use,

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both in this country as well
as in many other countries,

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and that would really help.

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A third option might include
something like tradeable permits,

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which are, we actually,

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and these seem like faraway scenarios,

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but if you consider the fact that we might not

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have antibiotics for many people who have infections,

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we might consider the fact that we might

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want to allocate who actually gets to use

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some of these antibiotics over others,

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and some of these might have to
be on the basis of clinical need,

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but also on the basis of pricing.

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And certainly consumer education works.

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Very often, people overuse antibiotics

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or prescribe too much without necessarily

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knowing that they do so,

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and feedback mechanisms

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have been found to be useful,

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both on energy —

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When you tell someone that they're using

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a lot of energy during peak hour,

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they tend to cut back,

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and the same sort of example has been performed

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even in the case of antibiotics.

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A hospital in St. Louis basically would put up

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on a chart the names of surgeons

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in the ordering of how much antibiotics they'd used

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in the previous month,

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and this was purely an informational feedback,

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there was no shaming,

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but essentially that provided some information back

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to surgeons that maybe they could rethink

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how they were using antibiotics.

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Now, there's a lot that can be done

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on the supply side as well.

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If you look at the price of penicillin,

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the cost per day is about 10 cents.

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It's a fairly cheap drug.

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If you take drugs that have
been introduced since then

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— linezolid or daptomycin —

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those are significantly more expensive,

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so to a world that has been used

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to paying 10 cents a day for antibiotics,

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the idea of paying 180 dollars per day

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seems like a lot.

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But what is that really telling us?

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That price is telling us

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that we should no longer

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take cheap, effective antibiotics as a given

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into the foreseeable future,

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and that price is a signal to us

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that perhaps we need to be paying

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much more attention to conservation.

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That price is also a signal

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that maybe we need to start
looking at other technologies,

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in the same way that gasoline prices are a signal

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and an impetus, to, say,

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the development of electric cars.

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Prices are important signals

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that we need to pay attention to,

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but we also need to consider the fact that

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although these high prices
seem unusual for antibiotics,

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they're nothing compared to the price per day

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of some cancer drugs,

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which might save a patient's life only
for a few months or perhaps a year,

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whereas antibiotics would potentially

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save a patient's life forever.

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So this is going to involve

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a whole new paradigm shift,

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and it's also a scary shift because

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in many parts of this country,

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in many parts of the world,

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the idea of paying 200 dollars

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for a day of antibiotic treatment

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is simply unimaginable.

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So we need to think about that.

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Now, there are backstop options,

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which is other alternative technologies

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that people are working on.

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It includes bacteriophages, probiotics,

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quorum sensing, synbiotics.

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Now, all of these are useful avenues to pursue,

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and they will become even more lucrative

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when the price of new antibiotics starts going higher,

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and we've seen that the
market does actually respond,

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and the government is now considering

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ways of subsidizing new antibiotics and development.

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But there are challenges here.

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We don't want to just throw money at a problem.

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What we want to be able to do

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is invest in new antibiotics

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in ways that actually encourage

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appropriate use and sales of those antibiotics,

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and that really is the challenge here.

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Now, going back to these technologies,

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you all remember the line from that famous

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dinosaur film, "Nature will find a way."

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So it's not as if these are permanent solutions.

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We really have to remember that,

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whatever the technology might be,

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that nature will find some way to work around it.

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You might, well, this is just a problem

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just with antibiotics and with bacteria,

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but it turns out that we have the exact same

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identical problem in many other fields as well,

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with multi-drug resistant tuberculosis,

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which is a serious problem in India and South Africa.

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Thousands of patients are dying because

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the second line drugs are so expensive,

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and in some instances, even those don't work

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and you have XDR TB.

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Viruses are become resistant.

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Agricultural pests. Malaria parasites.

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Right now, much of the world depends on

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one drug, artemisinin drugs,

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essentially to treat malaria.

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Resistance to artemisinin has already emerged,

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and if this were to become widespread,

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that puts at risk

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the single drug that we have to treat malaria

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around the world

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in a way that's currently safe an efficacious.

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Mosquitoes develop resistance.

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If you have kids, you probably know about head lice,

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and if you're from New York City, I understand that

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the specialty there is bedbugs.

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So those are also resistant.

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And we have to bring an
example from across the pond.

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Turns out that rats are also resistant to poisons.

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Now, what's common to all of these things is

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the idea that we've had these technologies

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to control nature only for the last 70, 80,

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or a hundred years,

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and essentially in a blink,

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we have squandered our ability to control,

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because we have not recognized

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that natural selection and evolution was going to find

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a way to get back,

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and we need to completely rethink

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how we're going to use

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measures to control biological organisms,

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and rethink how we incentivize

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the development, introduction,

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in the case of antibiotics prescription,

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and use of these valuable resources.

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And we really now need to start thinking about them

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as natural resources.

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And so that's, we stand at a crossroads.

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An option is to go through that rethinking

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and carefully consider incentives

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to change how we do business.

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The alternative is

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a world in which even a blade of grass

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is a potentially lethal weapon.

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Thank you.

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(Applause)