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The first patient to ever be 
treated with an antibiotic

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was a policeman in Oxford.

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On his day off from work,

4
00:00:07,800 --> 00:00:11,173
he was scratched by a rose thorn
while working in the garden.

5
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That small scratch became infected.

6
00:00:14,848 --> 00:00:17,163
Over the next few days, 
his head was swollen

7
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with abscesses,

8
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and in fact his eye was so infected

9
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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

15
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led by a Dr. Howard Florey

16
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had managed to synthesize

17
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a very small amount of penicillin,

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a drug that had been discovered

19
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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,

23
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but Florey and his team figured

24
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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,

27
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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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Second day, he was doing much better.

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They were 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 from his urine

35
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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,

42
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but fortunately for 
millions of other people,

43
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like this child who was treated 
again in the early 1940s,

44
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who was again dying of a sepsis,

45
00:01:53,740 --> 00:01:56,890
and within just six days, you can see,

46
00:01:56,890 --> 00:02:00,243
recovered thanks to this 
wonder drug, penicillin.

47
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Millions have lived,

48
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and global health has been transformed.

49
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Now, antibiotics have been used

50
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for patients like this,

51
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but they've also been 
used rather frivolously

52
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in some instances,

53
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for treating someone 
with just a cold or the flu,

54
00:02:17,949 --> 00:02:20,423
which they might not have 
responded to an antibiotic,

55
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and they've also been 
used in large quantities

56
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sub-therapeutically, which
means in small concentrations,

57
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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,

59
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we've spent a lot of 
antibiotics on animals,

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not for treatment, not for sick animals,

61
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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

65
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has imposed such large
selection pressure on bacteria

66
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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 is 
of carbapenem resistance in acinetobacter.

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Acinetobacter is a nasty hospital bug,

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and carbapenem is pretty much

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the strongest class of antibiotics

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that we can throw at this bug.

80
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And you can see in 1999

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this is the pattern of resistance,

82
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mostly under about 10 percent
across the United States.

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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,

85
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but wherever it is, it certainly is a lot worse now

86
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than it was in 1999,

87
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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,

90
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and at the heart of it, 
you might say, well,

91
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isn't this really just a medical issue?

92
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If we taught doctors how not 
to use antibiotics as much,

93
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if we taught patients how 
not to demand antibiotics,

94
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perhaps this really wouldn't be an issue,

95
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and maybe the pharmaceutical companies

96
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should be working harder to develop

97
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more antibiotics.

98
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Now, it turns out that there's something 
fundamental about antibiotics

99
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which makes it different from other drugs,

100
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which is that if I misuse antibiotics

101
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or I use antibiotics,

102
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not only am I affected but 
others are affected as well,

103
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in the same way as if I 
choose to drive to work

104
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or take a plane to go somewhere,

105
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that the costs I impose on others

106
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through global climate change go everywhere,

107
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and I don't necessarily take
these costs into consideration.

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This is what economists might 
call a problem of the commons,

109
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and the problem of the commons is exactly

110
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what we face in the case 
of antibiotics as well:

111
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that we don't consider —

112
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and we, including individuals, patients,

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hospitals, entire health systems —

114
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do not consider the costs 
that they impose on others

115
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by the way antibiotics are actually used.

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Now, that's a problem that's similar

117
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to another area that we all know about,

118
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which is of fuel use and energy,

119
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and of course energy use

120
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both depletes energy as well as

121
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leads to local pollution 
and climate change.

122
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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,

125
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and that's analogous to making better use

126
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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 
is to go find new antibiotics.

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Now, these are not separate.

132
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They're related, because if we invest heavily

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in new oil wells,

134
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we reduce the incentives 
for conservation of oil

135
00:05:51,760 --> 00:05:54,286
in the same way that's going 
to happen for antibiotics.

136
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The reverse is also going 
to happen, which is that

137
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if we use our antibiotics appropriately,

138
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we don't necessarily have 
to make the investments

139
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in new drug development.

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And if you thought that these two were entirely,

141
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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.

144
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The game is really one of coevolution,

145
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and coevolution is, in 
this particular picture,

146
00:06:18,116 --> 00:06:20,472
between cheetahs and gazelles.

147
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Cheetahs have evolved to run faster,

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because if they didn't run faster,

149
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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,

153
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except we're not the cheetahs,

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we're the gazelles,

155
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and the bacteria would,

156
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just in the course of this little talk,

157
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would have had kids and grandkids

158
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and figured out how to be resistant

159
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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,

166
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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,

181
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which means we're imposing 
the costs of pollution

182
00:07:38,249 --> 00:07:41,080
on people who actually use that energy.

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00:07:41,080 --> 00:07:44,060
We might consider doing that for antibiotics as well,

184
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and perhaps that would make sure that antibiotics

185
00:07:46,771 --> 00:07:49,172
actually get used appropriately.

186
00:07:49,172 --> 00:07:51,200
There are clean energy subsidies,

187
00:07:51,200 --> 00:07:54,255
which are to switch to fuels
which don't pollute as much

188
00:07:54,255 --> 00:07:57,100
or perhaps don't need fossil fuels.

189
00:07:57,100 --> 00:07:59,960
Now, the analogy here is, perhaps we need

190
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to move away from using antibiotics,

191
00:08:02,220 --> 00:08:05,936
and if you think about it, what are 
good substitutes for antibiotics?

192
00:08:05,936 --> 00:08:08,100
Well, turns out that anything that reduces

193
00:08:08,100 --> 00:08:10,343
the need for the antibiotic would really work,

194
00:08:10,343 --> 00:08:13,485
so that could include improving
hospital infection control

195
00:08:13,485 --> 00:08:16,380
or vaccinating people,

196
00:08:16,380 --> 00:08:18,677
particularly against 
the seasonal influenza.

197
00:08:18,677 --> 00:08:21,208
And the seasonal flu is probably

198
00:08:21,208 --> 00:08:24,212
the biggest driver of antibiotic use,

199
00:08:24,212 --> 00:08:27,131
both in this country as well
as in many other countries,

200
00:08:27,131 --> 00:08:29,151
and that could really help.

201
00:08:29,151 --> 00:08:33,254
A third option might include
something like tradeable permits.

202
00:08:33,254 --> 00:08:37,500
And these seem like faraway scenarios,

203
00:08:37,500 --> 00:08:39,927
but if you consider the 
fact that we might not

204
00:08:39,927 --> 00:08:43,310
have antibiotics for many 
people who have infections,

205
00:08:43,310 --> 00:08:45,547
we might consider the fact that we might

206
00:08:45,547 --> 00:08:47,858
want to allocate who actually gets to use

207
00:08:47,858 --> 00:08:50,572
some of these antibiotics over others,

208
00:08:50,572 --> 00:08:53,898
and some of these might have to
be on the basis of clinical need,

209
00:08:53,898 --> 00:08:55,833
but also on the basis of pricing.

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00:08:55,833 --> 00:08:57,743
And certainly consumer education works.

211
00:08:57,743 --> 00:09:00,344
Very often, people overuse antibiotics

212
00:09:00,344 --> 00:09:02,621
or prescribe too much without necessarily

213
00:09:02,621 --> 00:09:04,227
knowing that they do so,

214
00:09:04,227 --> 00:09:05,658
and feedback mechanisms

215
00:09:05,658 --> 00:09:07,560
have been found to be useful,

216
00:09:07,560 --> 00:09:09,489
both on energy —

217
00:09:09,489 --> 00:09:11,029
When you tell someone that they're using

218
00:09:11,029 --> 00:09:12,946
a lot of energy during peak hour,

219
00:09:12,946 --> 00:09:14,416
they tend to cut back,

220
00:09:14,416 --> 00:09:16,183
and the same sort of example has been performed

221
00:09:16,183 --> 00:09:17,993
even in the case of antibiotics.

222
00:09:17,993 --> 00:09:19,974
A hospital in St. Louis basically would put up

223
00:09:19,974 --> 00:09:24,166
on a chart the names of surgeons

224
00:09:24,166 --> 00:09:26,385
in the ordering of how much antibiotics they'd used

225
00:09:26,385 --> 00:09:28,329
in the previous month,

226
00:09:28,329 --> 00:09:30,671
and this was purely an 
informational feedback,

227
00:09:30,671 --> 00:09:31,854
there was no shaming,

228
00:09:31,854 --> 00:09:33,989
but essentially that provided 
some information back

229
00:09:33,989 --> 00:09:35,943
to surgeons that maybe they could rethink

230
00:09:35,943 --> 00:09:38,172
how they were using antibiotics.

231
00:09:38,172 --> 00:09:40,186
Now, there's a lot that can be done

232
00:09:40,186 --> 00:09:42,335
on the supply side as well.

233
00:09:42,335 --> 00:09:44,112
If you look at the price of penicillin,

234
00:09:44,112 --> 00:09:45,763
the cost per day is about 10 cents.

235
00:09:45,763 --> 00:09:47,521
It's a fairly cheap drug.

236
00:09:47,521 --> 00:09:49,658
If you take drugs that have
been introduced since then —

237
00:09:49,658 --> 00:09:52,302
linezolid or daptomycin —

238
00:09:52,302 --> 00:09:54,180
those are significantly more expensive,

239
00:09:54,180 --> 00:09:59,631
so to a world that has been used to
paying 10 cents a day for antibiotics,

240
00:09:59,633 --> 00:10:02,163
the idea of paying 180 dollars per day

241
00:10:02,163 --> 00:10:03,730
seems like a lot.

242
00:10:03,730 --> 00:10:05,717
But what is that really telling us?

243
00:10:05,717 --> 00:10:07,682
That price is telling us

244
00:10:07,682 --> 00:10:09,580
that we should no longer

245
00:10:09,580 --> 00:10:13,697
take cheap, effective 
antibiotics as a given

246
00:10:13,697 --> 00:10:15,464
into the foreseeable future,

247
00:10:15,464 --> 00:10:17,994
and that price is a signal to us

248
00:10:17,994 --> 00:10:19,603
that perhaps we need to be paying

249
00:10:19,603 --> 00:10:22,156
much more attention to conservation.

250
00:10:22,156 --> 00:10:24,860
That price is also a signal

251
00:10:24,860 --> 00:10:27,735
that maybe we need to start
looking at other technologies,

252
00:10:27,735 --> 00:10:30,387
in the same way that 
gasoline prices are a signal

253
00:10:30,387 --> 00:10:32,977
and an impetus, to, say,

254
00:10:32,977 --> 00:10:34,845
the development of electric cars.

255
00:10:34,845 --> 00:10:36,622
Prices are important signals

256
00:10:36,622 --> 00:10:38,208
and we need to pay attention,

257
00:10:38,208 --> 00:10:40,660
but we also need to consider the fact that

258
00:10:40,660 --> 00:10:44,912
although these high prices
seem unusual for antibiotics,

259
00:10:44,912 --> 00:10:47,151
they're nothing compared to the price per day

260
00:10:47,151 --> 00:10:48,535
of some cancer drugs,

261
00:10:48,535 --> 00:10:51,905
which might save a patient's life only
for a few months or perhaps a year,

262
00:10:51,905 --> 00:10:53,675
whereas antibiotics would potentially

263
00:10:53,675 --> 00:10:55,501
save a patient's life forever.

264
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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,
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 think, 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 multidrug-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 becoming 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 around the world

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in a way that's currently 
safe and efficacious.

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Mosquitos 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,

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00:13:10,968 --> 00:13:13,701
I understand that 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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00:13:18,835 --> 00:13:21,190
Turns out that rats are 
also resistant to poisons.

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00:13:21,190 --> 00:13:23,891
Now, what's common 
to all of these things is

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00:13:23,891 --> 00:13:26,597
the idea that we've had these technologies

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00:13:26,597 --> 00:13:31,218
to control nature only for 
the last 70, 80 or 100 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

331
00:13:42,100 --> 00:13:43,274
a way to get back,

332
00:13:43,274 --> 00:13:45,323
and we need to completely rethink

333
00:13:45,323 --> 00:13:47,666
how we're going to use

334
00:13:47,666 --> 00:13:50,760
measures to control biological organisms,

335
00:13:50,760 --> 00:13:54,224
and rethink how we incentivize

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00:13:54,224 --> 00:13:56,450
the development, introduction,

337
00:13:56,450 --> 00:13:59,118
in the case of antibiotics prescription,

338
00:13:59,118 --> 00:14:02,890
and use of these valuable resources.

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00:14:02,890 --> 00:14:05,270
And we really now need to 
start thinking about them

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00:14:05,270 --> 00:14:07,228
as natural resources.

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00:14:07,228 --> 00:14:09,466
And so we stand at a crossroads.

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00:14:09,466 --> 00:14:12,625
An option is to go through that rethinking

343
00:14:12,625 --> 00:14:14,438
and carefully consider incentives

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00:14:14,438 --> 00:14:16,992
to change how we do business.

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00:14:16,992 --> 00:14:19,253
The alternative is

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00:14:19,253 --> 00:14:22,336
a world in which even a blade of grass

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00:14:22,336 --> 00:14:24,765
is a potentially lethal weapon.

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00:14:24,765 --> 00:14:26,565
Thank you.

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00:14:26,565 --> 00:14:29,300
(Applause)