0:00:00.782,0:00:04.160
The first patient to be treated with an antibiotic

0:00:04.160,0:00:06.403
was a policeman from Oxford.

0:00:06.403,0:00:07.900
On his day off from work,

0:00:07.900,0:00:11.533
he was scratched by a rose thorn[br]while working in the garden.

0:00:11.533,0:00:14.848
That small scratch became infected.

0:00:14.848,0:00:17.163
Over the next few days, his head was swollen

0:00:17.163,0:00:18.884
with abscesses,

0:00:18.884,0:00:21.167
and in fact his eye was so infected

0:00:21.167,0:00:23.057
that they had to take it out,

0:00:23.057,0:00:26.038
and by February of 1941,

0:00:26.038,0:00:28.827
this poor man was on the verge of dying.

0:00:28.827,0:00:31.685
He was at Radcliffe Infirmary in Oxford,

0:00:31.685,0:00:33.991
and fortunately for him,

0:00:33.991,0:00:35.701
a small team of doctors

0:00:35.701,0:00:37.410
led by a Dr. Howard Florey

0:00:37.410,0:00:38.997
had managed to synthesize

0:00:38.997,0:00:41.820
a very small amount of penicillin,

0:00:41.820,0:00:43.901
a drug that had been discovered

0:00:43.901,0:00:46.223
12 years before by Alexander Fleming

0:00:46.223,0:00:49.930
but had never actually been used to treat a human,

0:00:49.930,0:00:52.720
and indeed no one even knew if the drug would work,

0:00:52.720,0:00:56.072
if it was full of impurities that would kill the patient,

0:00:56.072,0:00:57.894
but Florey and his team figured

0:00:57.894,0:00:59.616
if they had to use it, they might as well use it

0:00:59.616,0:01:02.181
on someone who was going to die anyway.

0:01:02.181,0:01:05.836
So they gave Albert Alexander,

0:01:05.836,0:01:08.715
this Oxford policeman, the drug,

0:01:08.715,0:01:11.132
and within 24 hours,

0:01:11.132,0:01:13.394
he started getting better.

0:01:13.394,0:01:18.060
His fever went down, his appetite came back.

0:01:18.060,0:01:20.613
Secondly, he was doing much better.

0:01:20.613,0:01:22.391
He was starting to run out of penicillin,

0:01:22.391,0:01:24.213
so what they would do was run with his urine

0:01:24.213,0:01:26.463
across the road to re-synthesize the penicillin

0:01:26.463,0:01:28.768
from his urine and give it back to him,

0:01:28.768,0:01:30.186
and that worked.

0:01:30.186,0:01:32.706
Day four, well on the way to recovery.

0:01:32.706,0:01:34.494
This was a miracle.

0:01:34.494,0:01:38.037
Day five, they ran out of penicillin,

0:01:38.037,0:01:40.637
and the poor man died.

0:01:40.637,0:01:43.089
So that story didn't end that well,

0:01:43.089,0:01:47.610
but fortunately for millions of other people

0:01:47.610,0:01:49.376
like this child who was treated again

0:01:49.376,0:01:51.221
in the early 1940s,

0:01:51.221,0:01:54.056
who was again dying of abscesses,

0:01:54.056,0:01:56.890
and within just six days, you can see,

0:01:56.890,0:02:00.243
recovered thanks to this wonder drug penicillin.

0:02:00.243,0:02:02.201
Millions have lived,

0:02:02.201,0:02:06.115
and global health has been transformed.

0:02:06.115,0:02:08.578
Now, antibiotics have been used

0:02:08.578,0:02:11.705
for patients like this,

0:02:11.705,0:02:13.842
but they've also been used rather frivolously

0:02:13.842,0:02:15.586
in some instances

0:02:15.586,0:02:17.949
for treating someone with just a cold or the flu

0:02:17.949,0:02:20.423
which they might not have responded to an antibiotic,

0:02:20.423,0:02:24.461
and they've also been used in large quantities

0:02:24.461,0:02:27.803
sub-therapeutically, which[br]means in small concentrations,

0:02:27.803,0:02:30.986
to make chicken and hogs grow faster.

0:02:30.986,0:02:34.552
Just to save a few pennies on the price of meat,

0:02:34.552,0:02:37.172
we've spent a lot of antibiotics on animals,

0:02:37.172,0:02:39.614
not for treatment, not for sick animals,

0:02:39.614,0:02:42.730
but primarily for growth promotion.

0:02:42.730,0:02:45.587
Now, what did that lead us to?

0:02:45.587,0:02:48.298
Basically, the massive use of antibiotics

0:02:48.298,0:02:50.143
around the world

0:02:50.143,0:02:53.697
has imposed such large[br]selection pressure on bacteria

0:02:53.697,0:02:56.059
that resistance is now a problem,

0:02:56.059,0:02:58.005
because we've now selected for just

0:02:58.005,0:02:59.985
the resistant bacteria.

0:02:59.985,0:03:03.315
And I'm sure you've all read[br]about this in the newspapers,

0:03:03.315,0:03:04.819
you've seen this in every magazine

0:03:04.819,0:03:06.528
that you come across,

0:03:06.528,0:03:08.328
but I really want you to appreciate

0:03:08.328,0:03:10.499
the significance of this problem.

0:03:10.499,0:03:11.950
This is serious.

0:03:11.950,0:03:13.806
The next slide I'm about to show you

0:03:13.806,0:03:17.035
is of carbapenum resistance in acinetobacter.

0:03:17.035,0:03:19.284
Acinetobacter is a nasty hospital bug,

0:03:19.284,0:03:20.747
and carbapenum is pretty much

0:03:20.747,0:03:22.265
the strongest class of antibiotics

0:03:22.265,0:03:25.111
that we can throw at this bug.

0:03:25.111,0:03:28.059
And you can see in 1999,

0:03:28.059,0:03:30.185
this is the pattern of resistance,

0:03:30.185,0:03:33.638
mostly under about 10 percent[br]across the United States.

0:03:33.638,0:03:37.215
Now watch what happens when we play the video.

0:03:46.461,0:03:48.516
So I don't know where you live,

0:03:48.516,0:03:51.418
but wherever it is, it certainly is a lot worse now

0:03:51.418,0:03:54.275
than it was in 1999,

0:03:54.275,0:03:57.886
and that is the problem of antibiotic resistance.

0:03:57.886,0:03:59.573
It's a global issue

0:03:59.573,0:04:02.511
affecting both rich and poor countries,

0:04:02.511,0:04:04.242
and at the heart of it, you might say, well,

0:04:04.242,0:04:06.210
isn't this really just a medical issue?

0:04:06.210,0:04:08.671
If we taught doctors of how[br]not to use antibiotics as much,

0:04:08.671,0:04:11.676
if we taught patients how not to demand antibiotics,

0:04:11.676,0:04:13.791
perhaps this really wouldn't be an issue,

0:04:13.791,0:04:15.580
and maybe the pharmaceutical companies

0:04:15.580,0:04:17.335
should be working harder to develop

0:04:17.335,0:04:19.101
more antibiotics.

0:04:19.101,0:04:20.720
Now, it turns out that there's something

0:04:20.720,0:04:22.622
fundamental about antibiotics

0:04:22.622,0:04:24.253
which make it different from other drugs,

0:04:24.253,0:04:25.874
which is that if I misuse antibiotics

0:04:25.874,0:04:27.701
or I use antibiotics,

0:04:27.701,0:04:31.291
not only am I affected but others are affected as well,

0:04:31.291,0:04:33.629
in the same as if I choose to drive to work

0:04:33.629,0:04:36.498
or take a plane to go somewhere,

0:04:36.498,0:04:38.242
that the costs I impose on others

0:04:38.242,0:04:40.682
through global climate change go everywhere,

0:04:40.682,0:04:43.585
and I don't necessarily take[br]these costs into consideration.

0:04:43.585,0:04:45.294
This is what economists might call

0:04:45.294,0:04:47.039
a problem of the commons,

0:04:47.039,0:04:48.714
and the problem of the commons is exactly

0:04:48.714,0:04:50.739
what we face in the case of antibiotics as well;

0:04:50.739,0:04:52.889
that we don't consider,

0:04:52.889,0:04:55.891
and we, including individuals, patients,

0:04:55.891,0:04:59.097
hospitals, entire health systems,

0:04:59.097,0:05:01.538
do not consider the costs that they impose on others

0:05:01.538,0:05:04.114
by the way antibiotics are actually used.

0:05:04.114,0:05:05.959
Now, that's a problem that's similar

0:05:05.959,0:05:08.281
to another area that we all know about,

0:05:08.281,0:05:10.075
which is of fuel use, and energy,

0:05:10.075,0:05:11.369
and of course energy use

0:05:11.369,0:05:14.451
both depletes energy as well as

0:05:14.451,0:05:18.103
leads to local pollution and climate change.

0:05:18.103,0:05:19.873
And typically, in the case of energy,

0:05:19.873,0:05:21.831
there are two ways in which[br]you can deal with the problem.

0:05:21.831,0:05:25.756
One is, we can make better[br]use of the oil that we have,

0:05:25.756,0:05:27.691
and that's analogous to making better use

0:05:27.691,0:05:29.549
of existing antibiotics,

0:05:29.549,0:05:31.280
and we can do this in a number of ways

0:05:31.280,0:05:33.091
that we'll talk about in a second,

0:05:33.091,0:05:36.847
but the other option is the "drill, baby, drill" option,

0:05:36.847,0:05:38.918
which in the case of antibiotics

0:05:38.918,0:05:41.044
is to go find new antibiotics.

0:05:41.044,0:05:43.001
Now, these are not separate.

0:05:43.001,0:05:46.522
They're related, because if we invest heavily

0:05:46.522,0:05:48.806
in new oil wells,

0:05:48.806,0:05:51.760
we reduce the incentives for conservation of oil

0:05:51.760,0:05:54.126
in the same way that's going to happen for antibiotics.

0:05:54.126,0:05:56.454
The reverse is also going to happen, which is that

0:05:56.454,0:05:58.792
if we use our antibiotics appropriately,

0:05:58.792,0:06:01.573
we don't necessarily have to make the investments

0:06:01.573,0:06:03.980
in new drug development.

0:06:03.980,0:06:06.466
And if you thought that these two were entirely,

0:06:06.466,0:06:08.288
fully balanced between these two options,

0:06:08.288,0:06:10.471
you might consider the fact that

0:06:10.471,0:06:12.743
this is really a game that we're playing.

0:06:12.743,0:06:15.184
The game is really one of coevolution,

0:06:15.184,0:06:18.116
and coevolution is, in this particular picture,

0:06:18.116,0:06:20.472
between cheetahs and gazelles.

0:06:20.472,0:06:22.025
Cheetahs have evolved to run faster,

0:06:22.025,0:06:23.667
because if they didn't run faster,

0:06:23.667,0:06:25.613
they wouldn't get any lunch.

0:06:25.613,0:06:28.065
Gazelles have evolved to run faster because

0:06:28.065,0:06:31.509
if they don't run faster, they would be lunch.

0:06:31.509,0:06:34.395
Now, this is the game we're[br]playing against the bacteria,

0:06:34.395,0:06:36.452
except we're not the cheetahs,

0:06:36.452,0:06:38.219
we're the gazelles,

0:06:38.219,0:06:40.716
and the bacteria would,

0:06:40.716,0:06:42.549
just in the course of this little talk,

0:06:42.549,0:06:44.315
would have had kids and grandkids

0:06:44.315,0:06:46.059
and figured out how to be resistant

0:06:46.059,0:06:49.164
just by selection and trial and error,

0:06:49.164,0:06:50.986
trying it over and over again.

0:06:50.986,0:06:54.518
Whereas how do we stay ahead of the bacteria?

0:06:54.518,0:06:56.802
We have drug discovery processes,

0:06:56.802,0:06:58.422
screening molecules,

0:06:58.422,0:07:00.042
we have clinical trials,

0:07:00.042,0:07:02.268
and then, when we think we have a drug,

0:07:02.268,0:07:05.823
then we have the FDA regulatory process.

0:07:05.823,0:07:08.231
And once we go through all of that,

0:07:08.231,0:07:10.266
then we try to stay one step ahead

0:07:10.266,0:07:12.932
of the bacteria.

0:07:12.932,0:07:15.339
Now, this is clearly not a game that can be sustained,

0:07:15.339,0:07:16.476
or one that we can win

0:07:16.476,0:07:18.703
by simply innovating to stay ahead.

0:07:18.703,0:07:21.988
We've got to slow the pace of coevolution down,

0:07:21.988,0:07:24.440
and there are ideas that we can borrow from energy

0:07:24.440,0:07:27.094
that are helpful in thinking about

0:07:27.094,0:07:28.827
how we might want to do this in the case

0:07:28.827,0:07:30.593
of antibiotics as well.

0:07:30.593,0:07:32.393
Now, if you think about how we deal with

0:07:32.393,0:07:34.136
energy pricing, for instance,

0:07:34.136,0:07:35.965
we consider emissions taxes,

0:07:35.965,0:07:38.249
which means we're imposing the costs of pollution

0:07:38.249,0:07:41.050
on people who actually use that energy.

0:07:41.050,0:07:44.009
We might consider doing that for antibiotics as well,

0:07:44.009,0:07:46.911
and perhaps that would make sure that antibiotics

0:07:46.911,0:07:49.172
actually get used appropriately.

0:07:49.172,0:07:51.062
There are clean energy subsidies,

0:07:51.062,0:07:54.425
which are to switch to fuels[br]which don't pollute as much

0:07:54.425,0:07:57.001
or perhaps don't need fossil fuels.

0:07:57.001,0:08:00.046
Now, the analogy here is perhaps we need

0:08:00.046,0:08:02.345
to move away from using antibiotics,

0:08:02.345,0:08:04.099
and if you think about it,

0:08:04.099,0:08:06.236
what are good substitutes for antibiotics?

0:08:06.236,0:08:08.002
Well, turns out that anything that reduces

0:08:08.002,0:08:10.343
the need for the antibiotic would really work,

0:08:10.343,0:08:13.975
so that could include improving[br]hospital infection control

0:08:13.975,0:08:16.090
or vaccinating people,

0:08:16.090,0:08:18.677
particularly against the seasonal influenza,

0:08:18.677,0:08:21.208
and the seasonal flu is probably

0:08:21.208,0:08:24.212
the biggest driver of antibiotic use,

0:08:24.212,0:08:27.441
both in this country as well[br]as in many other countries,

0:08:27.441,0:08:29.151
and that would really help.

0:08:29.151,0:08:31.615
A third option might include[br]something like tradeable permits,

0:08:31.615,0:08:33.494
which are, we actually,

0:08:33.494,0:08:37.160
and these seem like faraway scenarios,

0:08:37.160,0:08:39.927
but if you consider the fact that we might not

0:08:39.927,0:08:44.078
have antibiotics for many people who have infections,

0:08:44.078,0:08:45.777
we might consider the fact that we might

0:08:45.777,0:08:47.858
want to allocate who actually gets to use

0:08:47.858,0:08:50.782
some of these antibiotics over others,

0:08:50.782,0:08:53.898
and some of these might have to[br]be on the basis of clinical need,

0:08:53.898,0:08:55.833
but also on the basis of pricing.

0:08:55.833,0:08:57.993
And certainly consumer education works.

0:08:57.993,0:09:00.344
Very often, people overuse antibiotics

0:09:00.344,0:09:02.211
or prescribe too much without necessarily

0:09:02.211,0:09:04.737
knowing that they do so,

0:09:04.737,0:09:06.328
and feedback mechanisms

0:09:06.328,0:09:07.960
have been found to be useful,

0:09:07.960,0:09:09.769
both on energy —

0:09:09.769,0:09:11.509
When you tell someone that they're using

0:09:11.509,0:09:13.156
a lot of energy during peak hour,

0:09:13.156,0:09:14.416
they tend to cut back,

0:09:14.416,0:09:16.183
and the same sort of example has been performed

0:09:16.183,0:09:17.993
even in the case of antibiotics.

0:09:17.993,0:09:19.974
A hospital in St. Louis basically would put up

0:09:19.974,0:09:24.416
on a chart the names of surgeons

0:09:24.416,0:09:26.385
in the ordering of how much antibiotics they'd used

0:09:26.385,0:09:28.549
in the previous month,

0:09:28.549,0:09:30.671
and this was purely an informational feedback,

0:09:30.671,0:09:32.234
there was no shaming,

0:09:32.234,0:09:33.989
but essentially that provided some information back

0:09:33.989,0:09:35.943
to surgeons that maybe they could rethink

0:09:35.943,0:09:38.612
how they were using antibiotics.

0:09:38.612,0:09:40.536
Now, there's a lot that can be done

0:09:40.536,0:09:42.335
on the supply side as well.

0:09:42.335,0:09:44.112
If you look at the price of penicillin,

0:09:44.112,0:09:45.763
the cost per day is about 10 cents.

0:09:45.763,0:09:47.521
It's a fairly cheap drug.

0:09:47.521,0:09:49.658
If you take drugs that have[br]been introduced since then

0:09:49.658,0:09:52.302
— linezolid or daptomycin —

0:09:52.302,0:09:54.180
those are significantly more expensive,

0:09:54.180,0:09:56.461
so to a world that has been used

0:09:56.461,0:09:59.633
to paying 10 cents a day for antibiotics,

0:09:59.633,0:10:02.163
the idea of paying 180 dollars per day

0:10:02.163,0:10:04.068
seems like a lot.

0:10:04.068,0:10:05.857
But what is that really telling us?

0:10:05.857,0:10:07.682
That price is telling us

0:10:07.682,0:10:09.580
that we should no longer

0:10:09.580,0:10:13.697
take cheap, effective antibiotics as a given

0:10:13.697,0:10:15.464
into the foreseeable future,

0:10:15.464,0:10:17.994
and that price is a signal to us

0:10:17.994,0:10:19.603
that perhaps we need to be paying

0:10:19.603,0:10:22.156
much more attention to conservation.

0:10:22.156,0:10:25.047
That price is also a signal

0:10:25.047,0:10:27.735
that maybe we need to start[br]looking at other technologies,

0:10:27.735,0:10:30.207
in the same way that gasoline prices are a signal

0:10:30.207,0:10:32.977
and an impetus, to, say,

0:10:32.977,0:10:34.845
the development of electric cars.

0:10:34.845,0:10:36.622
Prices are important signals

0:10:36.622,0:10:38.388
that we need to pay attention to,

0:10:38.388,0:10:40.660
but we also need to consider the fact that

0:10:40.660,0:10:44.912
although these high prices[br]seem unusual for antibiotics,

0:10:44.912,0:10:47.151
they're nothing compared to the price per day

0:10:47.151,0:10:48.535
of some cancer drugs,

0:10:48.535,0:10:51.955
which might save a patient's life only[br]for a few months or perhaps a year,

0:10:51.955,0:10:53.675
whereas antibiotics would potentially

0:10:53.675,0:10:55.621
save a patient's life forever.

0:10:55.621,0:10:56.960
So this is going to involve

0:10:56.960,0:10:58.782
a whole new paradigm shift,

0:10:58.782,0:11:00.638
and it's also a scary shift because

0:11:00.638,0:11:02.967
in many parts of this country,

0:11:02.967,0:11:04.711
in many parts of the world,

0:11:04.711,0:11:06.780
the idea of paying 200 dollars

0:11:06.780,0:11:09.671
for a day of antibiotic treatment

0:11:09.671,0:11:12.213
is simply unimaginable.

0:11:12.213,0:11:13.947
So we need to think about that.

0:11:13.947,0:11:15.760
Now, there are backstop options,

0:11:15.760,0:11:18.436
which is other alternative technologies

0:11:18.436,0:11:20.022
that people are working on.

0:11:20.022,0:11:22.282
It includes bacteriophages, probiotics,

0:11:22.282,0:11:26.084
quorum sensing, synbiotics.

0:11:26.084,0:11:29.369
Now, all of these are useful avenues to pursue,

0:11:29.369,0:11:31.259
and they will become even more lucrative

0:11:31.259,0:11:35.095
when the price of new antibiotics starts going higher,

0:11:35.095,0:11:37.987
and we've seen that the[br]market does actually respond,

0:11:37.987,0:11:40.145
and the government is now considering

0:11:40.145,0:11:43.802
ways of subsidizing new antibiotics and development.

0:11:43.802,0:11:45.455
But there are challenges here.

0:11:45.455,0:11:47.031
We don't want to just throw money at a problem.

0:11:47.031,0:11:48.669
What we want to be able to do

0:11:48.669,0:11:50.468
is invest in new antibiotics

0:11:50.468,0:11:53.944
in ways that actually encourage

0:11:53.944,0:11:56.824
appropriate use and sales of those antibiotics,

0:11:56.824,0:11:59.287
and that really is the challenge here.

0:11:59.287,0:12:01.616
Now, going back to these technologies,

0:12:01.616,0:12:03.979
you all remember the line from that famous

0:12:03.979,0:12:06.205
dinosaur film, "Nature will find a way."

0:12:06.205,0:12:09.524
So it's not as if these are permanent solutions.

0:12:09.524,0:12:12.134
We really have to remember that,

0:12:12.134,0:12:14.012
whatever the technology might be,

0:12:14.012,0:12:16.836
that nature will find some way to work around it.

0:12:16.836,0:12:18.557
You might, well, this is just a problem

0:12:18.557,0:12:21.301
just with antibiotics and with bacteria,

0:12:21.301,0:12:23.247
but it turns out that we have the exact same

0:12:23.247,0:12:25.981
identical problem in many other fields as well,

0:12:25.981,0:12:28.933
with multi-drug resistant tuberculosis,

0:12:28.933,0:12:32.495
which is a serious problem in India and South Africa.

0:12:32.495,0:12:34.282
Thousands of patients are dying because

0:12:34.282,0:12:36.116
the second line drugs are so expensive,

0:12:36.116,0:12:38.343
and in some instances, even those don't work

0:12:38.343,0:12:40.413
and you have XDR TB.

0:12:40.413,0:12:42.224
Viruses are become resistant.

0:12:42.224,0:12:45.063
Agricultural pests. Malaria parasites.

0:12:45.063,0:12:47.173
Right now, much of the world depends on

0:12:47.173,0:12:51.072
one drug, artemisinin drugs,

0:12:51.072,0:12:52.826
essentially to treat malaria.

0:12:52.826,0:12:55.413
Resistance to artemisinin has already emerged,

0:12:55.413,0:12:57.767
and if this were to become widespread,

0:12:57.767,0:12:59.485
that puts at risk

0:12:59.485,0:13:01.116
the single drug that we have to treat malaria

0:13:01.116,0:13:02.918
around the world

0:13:02.918,0:13:05.094
in a way that's currently safe an efficacious.

0:13:05.094,0:13:07.238
Mosquitoes develop resistance.

0:13:07.238,0:13:09.195
If you have kids, you probably know about head lice,

0:13:09.195,0:13:12.233
and if you're from New York City, I understand that

0:13:12.233,0:13:13.999
the specialty there is bedbugs.

0:13:13.999,0:13:15.956
So those are also resistant.

0:13:15.956,0:13:18.835
And we have to bring an[br]example from across the pond.

0:13:18.835,0:13:21.074
Turns out that rats are also resistant to poisons.

0:13:21.074,0:13:23.751
Now, what's common to all of these things is

0:13:23.751,0:13:26.597
the idea that we've had these technologies

0:13:26.597,0:13:30.278
to control nature only for the last 70, 80,

0:13:30.278,0:13:31.963
or a hundred years,

0:13:31.963,0:13:34.246
and essentially in a blink,

0:13:34.246,0:13:37.137
we have squandered our ability to control,

0:13:37.137,0:13:39.288
because we have not recognized

0:13:39.288,0:13:42.001
that natural selection and evolution was going to find

0:13:42.001,0:13:43.684
a way to get back,

0:13:43.684,0:13:45.743
and we need to completely rethink

0:13:45.743,0:13:47.666
how we're going to use

0:13:47.666,0:13:50.760
measures to control biological organisms,

0:13:50.760,0:13:54.224
and rethink how we incentivize

0:13:54.224,0:13:56.710
the development, introduction,

0:13:56.710,0:13:59.118
in the case of antibiotics prescription,

0:13:59.118,0:14:03.370
and use of these valuable resources.

0:14:03.370,0:14:05.270
And we really now need to start thinking about them

0:14:05.270,0:14:07.228
as natural resources.

0:14:07.228,0:14:09.466
And so that's, we stand at a crossroads.

0:14:09.466,0:14:12.625
An option is to go through that rethinking

0:14:12.625,0:14:14.438
and carefully consider incentives

0:14:14.438,0:14:16.992
to change how we do business.

0:14:16.992,0:14:19.253
The alternative is

0:14:19.253,0:14:22.436
a world in which even a blade of grass

0:14:22.436,0:14:24.765
is a potentially lethal weapon.

0:14:24.765,0:14:26.565
Thank you.

0:14:26.565,0:14:29.030
(Applause)