Ramanan Laxminarayan: The coming crisis in antibiotics

105,415 views ・ 2014-11-10

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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,
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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,
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and in fact his eye was so infected
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that they had to take it out,
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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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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
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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,
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but fortunately for millions of other people,
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like this child who was treated again in the early 1940s,
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who was again dying of a sepsis,
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and within just six days, you can see,
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recovered thanks to this wonder drug, penicillin.
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Millions have lived,
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and global health has been transformed.
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Now, antibiotics have been used
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for patients like this,
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but they've also been used rather frivolously
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in some instances,
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for treating someone with just a cold or the flu,
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which they might not have responded to an antibiotic,
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and they've also been used in large quantities
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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 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.
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And you can see in 1999
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this is the pattern of resistance,
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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,
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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,
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and at the heart of it, you might say, well,
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isn't this really just a medical issue?
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If we taught doctors how not to use antibiotics as much,
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if we taught patients how not to demand antibiotics,
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perhaps this really wouldn't be an issue,
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and maybe the pharmaceutical companies
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should be working harder to develop
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more antibiotics.
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Now, it turns out that there's something fundamental about antibiotics
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which makes it different from other drugs,
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which is that if I misuse antibiotics
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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 way 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 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 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, 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 could really help.
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A third option might include something like tradeable permits.
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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 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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and we need to pay attention,
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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, 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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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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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 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
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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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14:14
And we really now need to start thinking about them
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as natural resources.
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And so we stand at a crossroads.
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An option is to go through that rethinking
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14:24
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)
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