Ramanan Laxminarayan: The coming crisis in antibiotics

翻译人员: Yolanda Zhang 校对人员: Rocky LIANG

The first patient to ever be treated with an antibiotic

第一位接受抗生素治疗的患者

was a policeman in Oxford.

是一位来自牛津的警察。

On his day off from work,

有一天他下班后，

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

在花园劳作时被一朵玫瑰上的刺划伤了。

That small scratch became infected.

这个小伤口被感染了。

Over the next few days, his head was swollen

在接下来的几天里，他的脸开始浮胀

with abscesses,

并出现了脓肿，

and in fact his eye was so infected

事实上他的眼球也被感染了，

that they had to take it out,

不得不摘除。

and by February of 1941,

到了1941年的2月，

this poor man was on the verge of dying.

这个可怜的人已经奄奄一息了。

He was at Radcliffe Infirmary in Oxford,

他在牛津市的Radcliffe Infirmary 医院接受治疗，

and fortunately for him,

幸运的是，

a small team of doctors

由霍华德·弗洛里医生 （译注：澳洲药理学家）

led by a Dr. Howard Florey

带头的一个医疗小组

had managed to synthesize

成功的合成了

a very small amount of penicillin,

少量的盘尼西林，

a drug that had been discovered

一种被亚历山大·弗莱明 （译注：苏格兰药学家）

12 years before by Alexander Fleming

在12年前发现的药物，

but had never actually been used to treat a human,

但它从来没有被用来给人治病，

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

事实上甚至没有人知道 这种药是否有效，

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

如果这种药不纯净是否会致死，

but Florey and his team figured

但是弗洛里和他的团队觉得

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

如果他们需要使用这种药，不妨干脆在

on someone who was going to die anyway.

已无药可救的患者身上试试看。

So they gave Albert Alexander,

于是他们把这种药用在了

this Oxford policeman, the drug,

Albert Alexander这名 牛津警察的身上，

and within 24 hours,

还不到24小时，

he started getting better.

他的病情就开始逐渐好转。

His fever went down, his appetite came back.

他的烧退了，食欲也恢复了。

Second day, he was doing much better.

第二天，他恢复的更快了。

They were starting to run out of penicillin,

不过盘尼西林快用完了，

so what they would do was run with his urine

于是医生们提取了他的尿液

across the road to re-synthesize the penicillin from his urine

来重新合成盘尼西林，

and give it back to him,

再回过头来治疗他，

and that worked.

这种做法见效了。

Day four, well on the way to recovery.

第四天，他仍在慢慢好转。

This was a miracle.

这是个奇迹。

Day five, they ran out of penicillin,

第五天，盘尼西林又用完了，

and the poor man died.

这个可怜的人就死了。

So that story didn't end that well,

所以这个故事的结局不太好，

but fortunately for millions of other people,

但是对其他几百万人来说却是个福音，

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

比如这个在40年代同样接受 盘尼西林治疗的孩子，

who was again dying of a sepsis,

她差点死于败血症，

and within just six days, you can see,

但经过了仅仅6天的治疗，你们可以看到，

recovered thanks to this wonder drug, penicillin.

在神奇的盘尼西林的治疗下 她已经康复。

Millions have lived,

几百万人因此活了下来，

and global health has been transformed.

全球的健康状况也发生了转变。

Now, antibiotics have been used

现在，抗生素已经被用在

for patients like this,

这样的病人身上，

but they've also been used rather frivolously

但同时也应用于其他

in some instances,

非常不合适的情况，

for treating someone with just a cold or the flu,

比如仅仅用来治疗感冒或者流感，

which they might not have responded to an antibiotic,

而这很可能没什么效果，

and they've also been used in large quantities

抗生素也以非治疗的目的 被大量使用，

sub-therapeutically, which means in small concentrations,

也就是说用很低的浓度，

to make chicken and hogs grow faster.

让鸡和猪长得更快。

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

只为了买肉的时候省几分钱，

we've spent a lot of antibiotics on animals,

我们把大量的抗生素用在了动物身上，

not for treatment, not for sick animals,

但不是为了治疗， 并没有用在生病的动物身上，

but primarily for growth promotion.

而主要是促进生长。

Now, what did that lead us to?

那么，长此以往会怎么样呢？

Basically, the massive use of antibiotics

简单的说，世界范围内的

around the world

抗生素滥用

has imposed such large selection pressure on bacteria

已经导致其对很多细菌不起作用了，

that resistance is now a problem,

抗药性已经成为了一个问题，

because we've now selected for just

因为我们如今所针对的细菌

the resistant bacteria.

恰恰都具备了抗药性。

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

我很确定你们都在报纸上 看到过这个信息，

you've seen this in every magazine

你们浏览的每本杂志

that you come across,

也都提到了，

but I really want you to appreciate

不过我真的希望你们能够认识到

the significance of this problem.

这个问题的重要性。

This is serious.

情况已经很严重了。

The next slide I'm about to show you is of carbapenem resistance in acinetobacter.

在下一张幻灯片我要提到 不动杆菌对碳青霉烯的抗药性。

Acinetobacter is a nasty hospital bug,

不动杆菌是一种极易附着在 医疗材料上的细菌，

and carbapenem is pretty much

而碳青霉烯几乎是一种

the strongest class of antibiotics

我们可用来对付这种细菌的

that we can throw at this bug.

最强的抗生素。

And you can see in 1999

你们可以看到在1999年，

this is the pattern of resistance,

这种细菌抗药性在全美国的分布，

mostly under about 10 percent across the United States.

细菌抗药性只低于10%。

Now watch what happens when we play the video.

现在我们看看视频里发生了哪些变化。

So I don't know where you live,

我不知道你们都住在哪里，

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

不过无论在哪，情况都比1999年

than it was in 1999,

糟糕得多，

and that is the problem of antibiotic resistance.

这就是抗生素耐菌性问题。

It's a global issue

这是个全球性的问题，

affecting both rich and poor countries,

很多国家，不论穷富都受到了影响，

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

究其本质，你们可能会想，

isn't this really just a medical issue?

这应该只是个医疗问题吧？

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

如果我们告诉医生们 如何尽量少用抗生素，

if we taught patients how not to demand antibiotics,

如果我们告诉患者如何降低 对抗生素的依赖，

perhaps this really wouldn't be an issue,

这很有可能就不是个问题了，

and maybe the pharmaceutical companies

可能制药公司

should be working harder to develop

需要加大力度生产

more antibiotics.

更多的抗生素。

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

现在事实已经证明了抗生素 具备一些基本性质

which makes it different from other drugs,

让它不同于其他药物，

which is that if I misuse antibiotics

也就是说如果我误用了抗生素，

or I use antibiotics,

或者我仅仅是使用了抗生素，

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

不光是我自己，其他人也会受到影响，

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

就好比我决定开车去上班，

or take a plane to go somewhere,

或者飞去什么地方，

that the costs I impose on others

我的出行造成的气候变化

through global climate change go everywhere,

对其他人的影响无处不在，

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

我并不会意识到由此产生的代价。

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

这就是经济学家们所谓的公地问题，

and the problem of the commons is exactly

这种公地问题恰恰就是

what we face in the case of antibiotics as well:

我们在抗生素使用上需要面对的：

that we don't consider —

我们并没有考虑到——

and we, including individuals, patients,

这里的我们包括个人，患者，

hospitals, entire health systems —

医院，整个卫生系统——

do not consider the costs that they impose on others

没有认识到抗生素的实际使用方式

by the way antibiotics are actually used.

对其他人造成的影响。

Now, that's a problem that's similar

这个问题同另一个众所周知的

to another area that we all know about,

领域非常相似，

which is of fuel use and energy,

也就是燃料的使用以及能源，

and of course energy use

当然，能源的使用

both depletes energy as well as

不单大量的消耗了能源，同时也

leads to local pollution and climate change.

导致了地域性的空气污染和气候变化。

And typically, in the case of energy,

具体点说，在能源这个问题上，

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

有两种方法可以解决。

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

一个就是我们可以更好的 利用现有的原油，

and that's analogous to making better use

也就是说我们同样可以更好的利用

of existing antibiotics,

现有的抗生素，

and we can do this in a number of ways

可以通过很多种方法，

that we'll talk about in a second,

不胜枚举，

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

不过另一个选择就是所谓的 “不断开采”方式，

which in the case of antibiotics is to go find new antibiotics.

在抗生素的问题上就是 找到新的抗生素。

Now, these are not separate.

如今这两个问题已经不能区别对待了。

They're related, because if we invest heavily

它们是相互关联的， 因为如果我们大量的

in new oil wells,

开采新的油田，

we reduce the incentives for conservation of oil

我们就削弱了保护原油资源的动力，

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

对待抗生素也是如此。

The reverse is also going to happen, which is that

相反的情况也同样会发生，也就是

if we use our antibiotics appropriately,

如果我们适当的使用抗生素，

we don't necessarily have to make the investments

在新药研发领域

in new drug development.

也就不需要什么投资了。

And if you thought that these two were entirely,

如果你觉得这两点在这两个选择中

fully balanced between these two options,

可以完全平衡，

you might consider the fact that

你们可能会想到事实上

this is really a game that we're playing.

我们在玩一个游戏。

The game is really one of coevolution,

这个游戏类似于共同进化，

and coevolution is, in this particular picture,

而共同进化在这幅图片中就是

between cheetahs and gazelles.

非洲猎豹和瞪羚的关系。

Cheetahs have evolved to run faster,

非洲猎豹已经进化到能够跑得更快，

because if they didn't run faster,

因为如果它们不跑的再快一些，

they wouldn't get any lunch.

它们就吃不到午餐。

Gazelles have evolved to run faster because

瞪羚也进化的跑得更快了，

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

因为如果它们不跑快点， 就会被吃掉。

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

这就是我们要跟抗生素做的斗争，

except we're not the cheetahs,

只不过我们不是非洲猎豹，

we're the gazelles,

我们是瞪羚，

and the bacteria would,

而细菌们在

just in the course of this little talk,

演讲的这段时间里

would have had kids and grandkids

就已经繁殖了一代又一代，

and figured out how to be resistant

弄清了如何通过筛选，尝试和误差

just by selection and trial and error,

来变得更顽强，

trying it over and over again.

不断的进行尝试，变化。

Whereas how do we stay ahead of the bacteria?

那么我们要如何抢在细菌前面呢？

We have drug discovery processes,

我们有药物研究过程，

screening molecules,

筛选分子，

we have clinical trials,

我们有临床试验，

and then, when we think we have a drug,

当我们认为研制出了一种新药，

then we have the FDA regulatory process.

还要通过食品药物管理局的监管流程。

And once we go through all of that,

一旦我们经历了这些过程，

then we try to stay one step ahead

我们就会尝试更进一步

of the bacteria.

对付细菌。

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

显然这并不是一个能够长期进行的游戏，

or one that we can win

或者仅仅通过革新

by simply innovating to stay ahead.

就能保持领先优势。

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

我们需要减慢共同进化的脚步，

and there are ideas that we can borrow from energy

我们可以从能源领域借鉴一些想法，

that are helpful in thinking about

能够帮助我们思考

how we might want to do this in the case

我们应该如何

of antibiotics as well.

应对抗生素。

Now, if you think about how we deal with

如果你们想想我们是如何应对

energy pricing, for instance,

能源价格上涨，打个比方，

we consider emissions taxes,

我们考虑一下排放税，

which means we're imposing the costs of pollution

也就是说我们在向使用了那些能源的

on people who actually use that energy.

人们征税。

We might consider doing that for antibiotics as well,

我们会想要用同样的方式对待抗生素，

and perhaps that would make sure that antibiotics

这样可能会保证

actually get used appropriately.

抗生素能得到合理的使用。

There are clean energy subsidies,

洁净能源补贴

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

用在不会产生太多污染的燃料上，

or perhaps don't need fossil fuels.

或者可能完全不需要化石燃料。

Now, the analogy here is, perhaps we need

现在，相似的地方就是，可能我们需要

to move away from using antibiotics,

避免使用抗生素，

and if you think about it, what are good substitutes for antibiotics?

你们想一下，抗生素有哪些好的替代品？

Well, turns out that anything that reduces

任何可以减少对抗生素需求

the need for the antibiotic would really work,

的东西可能都行得通，

so that could include improving hospital infection control

也就是说可能包括提高医院的感染控制能力，

or vaccinating people,

或者给人们注射疫苗，

particularly against the seasonal influenza.

尤其是针对季节性流感。

And the seasonal flu is probably

季节性流感可能

the biggest driver of antibiotic use,

是抗生素使用的最大诱因，

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

不单是在我们国家，在其他国家也一样，

and that could really help.

这很有帮助。

A third option might include something like tradeable permits.

第三种选择可能包括可交易许可之类的东西。

And these seem like faraway scenarios,

这些看起来像遥不可及的计划，

but if you consider the fact that we might not

但是如果你们思考一下这个事实， 我们可能

have antibiotics for many people who have infections,

没有足够的抗生素让所有 受到感染的人都用上，

we might consider the fact that we might

我们可能考虑到一个事实，

want to allocate who actually gets to use

可能想要把这些抗生素分配给

some of these antibiotics over others,

那些更需要的人，

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

而其中一些人需要考虑临床需要

but also on the basis of pricing.

以及价格。

And certainly consumer education works.

当然消费者教育起了作用。

Very often, people overuse antibiotics

多数时候，人们用了过量的抗生素，

or prescribe too much without necessarily

或者开了太多处方，而并没有意识到

knowing that they do so,

他们确实做的过头了，

and feedback mechanisms

而反馈机制

have been found to be useful,

也被证明很有用，

both on energy —

对能源来说也是一样——

When you tell someone that they're using

当你跟别人说他们在高峰时间段

a lot of energy during peak hour,

耗费了太多能源，

they tend to cut back,

他们会开始节约，

and the same sort of example has been performed

同样的例子在抗生素上

even in the case of antibiotics.

也有所体现。

A hospital in St. Louis basically would put up

圣路易斯的一家医院简单的

on a chart the names of surgeons

把外科医生的名字依据

in the ordering of how much antibiotics they'd used

上个月用了多少抗生素

in the previous month,

列了个表，

and this was purely an informational feedback,

这就是个直接的信息反馈，

there was no shaming,

没什么可丢人的，

but essentially that provided some information back

不过重要的是这样做反馈给了

to surgeons that maybe they could rethink

外科大夫一些信息， 可能他们能够重新考虑

how they were using antibiotics.

如何使用抗生素。

Now, there's a lot that can be done

如今，在供给这方面

on the supply side as well.

也有不少可以采取的行动。

If you look at the price of penicillin,

如果你们看看盘尼西林的价格，

the cost per day is about 10 cents.

每一天的花费是10美分。

It's a fairly cheap drug.

这已经很便宜了。

If you take drugs that have been introduced since then —

如果你们吃同一时期上市的药——

linezolid or daptomycin —

利奈唑胺或者达托霉素——

those are significantly more expensive,

它们都要贵得多，

so to a world that has been used to paying 10 cents a day for antibiotics,

所以对于一个习惯了每天花费 10美分在抗生素上的

the idea of paying 180 dollars per day

市场来说，每天花180美元

seems like a lot.

看起来太多了。

But what is that really telling us?

那么这究竟告诉了我们什么呢？

That price is telling us

这个价格告诉了我们

that we should no longer

我们在可预见的未来

take cheap, effective antibiotics as a given

不应该继续使用

into the foreseeable future,

廉价有效的抗生素了，

and that price is a signal to us

这个价格对我们来说也是个信号，

that perhaps we need to be paying

可能我们需要对节俭保护

much more attention to conservation.

给予重视。

That price is also a signal

这个价格也给出了另外一个信号，

that maybe we need to start looking at other technologies,

可能我们需要开始转向其他技术，

in the same way that gasoline prices are a signal

就好像汽油价格是一种信号，

and an impetus, to, say,

可以说其

the development of electric cars.

刺激了电动车的发展。

Prices are important signals

价格是很重要的信号，

and we need to pay attention,

我们要重视起来，

but we also need to consider the fact that

但我们也要考虑到一个事实，

although these high prices seem unusual for antibiotics,

虽然这些高价对抗生素来说 看起来不太寻常，

they're nothing compared to the price per day

跟一些抗癌药的日常价格

of some cancer drugs,

相比抗生素的花销算不了什么，

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

抗癌药可以让患者的生命 多维持几个月或者一年，

whereas antibiotics would potentially

而抗生素很可能

save a patient's life forever.

彻底挽救一个患者的生命。

So this is going to involve

所以这将会包括

a whole new paradigm shift,

一个全新的模式变革

and it's also a scary shift because

这种变化也很可怕，因为

in many parts of this country,

在这个国家的很多地方，

in many parts of the world,

在世界的各个角落，

the idea of paying 200 dollars

每天花上200美元

for a day of antibiotic treatment

来进行抗生素治疗

is simply unimaginable.

简直是不可想象。

So we need to think about that.

所以我们需要好好想一想。

Now, there are backstop options,

还有一些强化方案，

which is other alternative technologies

也就是人们正在努力研究的

that people are working on.

很多其他技术。

It includes bacteriophages, probiotics,

包括噬菌体，益生菌，

quorum sensing, synbiotics.

细菌群体行为调控机制，合生剂。

Now, all of these are useful avenues to pursue,

现如今这些都是可以探寻的有效途径，

and they will become even more lucrative

当新的抗生素的价格不断上涨时，

when the price of new antibiotics starts going higher,

它们就会变得越来越盈利，

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

事实上市场已经开始有所回应了，

and the government is now considering

政府现在正在考虑

ways of subsidizing new antibiotics and development.

为新的抗生素及其研发提供补助。

But there are challenges here.

不过还有些挑战。

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

我们可不想把钱都花在麻烦上面。

What we want to be able to do

我们想要做的是

is invest in new antibiotics

投资新的抗生素，

in ways that actually encourage

能够实际上鼓励

appropriate use and sales of those antibiotics,

这些抗生素的适度使用和销售，

and that really is the challenge here.

这就是真正的挑战。

Now, going back to these technologies,

那么现在回到这些技术上，

you all remember the line from that famous

你们肯定都记得《侏罗纪公园》里的

dinosaur film, "Nature will find a way."

台词，“大自然会自寻出路。”

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

所以这看起来并不像个 一劳永逸的解决方案。

We really have to remember that, whatever the technology might be,

我们需要谨记，无论采用什么样的技术，

that nature will find some way to work around it.

大自然都会找到方法解决问题。

You might think, well, this is just a problem

你们可能会想，这只是个有关

just with antibiotics and with bacteria,

抗生素和细菌的问题，

but it turns out that we have the exact same

不过事实证明我们在很多其他领域

identical problem in many other fields as well,

都有相同的问题，

with multidrug-resistant tuberculosis,

比如对很多药物都有耐药性的肺结核，

which is a serious problem in India and South Africa.

这种病在印度和南非的状况不容乐观。

Thousands of patients are dying because

数以千计的患者都在面临死亡的威胁，

the second-line drugs are so expensive,

因为二线药物都很贵，

and in some instances, even those don't work

有的情况下，当你患有这种病时

and you have XDR TB.

它们甚至完全不起作用。

Viruses are becoming resistant.

病毒也在变得更耐药。

Agricultural pests. Malaria parasites.

农业害虫。疟原虫。

Right now, much of the world depends on

现在，世界上很多地方都依赖一种药，

one drug, artemisinin drugs,

青蒿素药物，

essentially to treat malaria.

尤其是用它来治疗疟疾。

Resistance to artemisinin has already emerged,

青蒿素耐菌性已经开始减弱了，

and if this were to become widespread,

如果这种情况愈演愈烈，

that puts at risk

单一药物的风险

the single drug that we have to treat malaria around the world

就会在全世界出现出现， 我们就需要采取目前看来安全有效的方式

in a way that's currently safe and efficacious.

来治疗疟疾。

Mosquitos develop resistance.

蚊子也变得耐药了。

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

如果你有孩子，你可能知道头虱，

and if you're from New York City,

如果你从纽约市来，

I understand that the specialty there is bedbugs.

我知道那里的臭虫问题很严重。

So those are also resistant.

这些东西都有耐药性。

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

我们需要借鉴一洋之隔的例子。

Turns out that rats are also resistant to poisons.

事实证明老鼠对毒药也产生了耐性。

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

那么所有这些事的共同点就是

the idea that we've had these technologies

我们用现有的技术

to control nature only for the last 70, 80 or 100 years

控制大自然的力量仅仅有七八十， 或者一百年左右，

and essentially in a blink,

而重点在于短时间内，

we have squandered our ability to control,

我们就浪费了真正能 掌控大自然的能力

because we have not recognized

因为我们还没有认识到

that natural selection and evolution was going to find

自然选择和进化会找到

a way to get back,

恢复原状的途径，

and we need to completely rethink

我们需要彻底重新考虑

how we're going to use

应该如何

measures to control biological organisms,

采取行动来控制生物体，

and rethink how we incentivize

重新考虑我们要如何实质性的促进

the development, introduction,

发展和新型药物的引入，

in the case of antibiotics prescription,

比如抗生素药物处方，

and use of these valuable resources.

以及如何使用这些珍贵的资源。

And we really now need to start thinking about them

我们现在真的需要把它们

as natural resources.

当成自然资源。

And so we stand at a crossroads.

我们正站在一个岔路口。

An option is to go through that rethinking

一种选择就是重新思考，

and carefully consider incentives

谨慎的考虑相关的动机

to change how we do business.

来改变我们的行事方式。

The alternative is

另一种情况就是

a world in which even a blade of grass

即便只是一片草叶子

is a potentially lethal weapon.

都可能成为一个世界的致命武器。

Thank you.

谢谢大家。

(Applause)

（掌声）