Ramanan Laxminarayan: The coming crisis in antibiotics

譯者: Yamei Huang 審譯者: Regina Chu

The first patient to ever be treated with an antibiotic

第一位接受抗生素治療的患者

was a policeman in Oxford.

是一位牛津的警察。

On his day off from work,

有一天，他休假在家，

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

整理自家花園時被玫瑰的刺劃傷。

That small scratch became infected.

那個小的傷口被感染了。

Over the next few days, his head was swollen

在接下來的幾天裡，他的頭因為膿瘡

with abscesses,

而腫了起來，

and in fact his eye was so infected

事實上他的眼睛受到嚴重感染，

that they had to take it out,

醫生只好將它摘除，

and by February of 1941,

到了 1941 年二月，

this poor man was on the verge of dying.

這個可憐的警察 已經徘徊在生死邊緣。

He was at Radcliffe Infirmary in Oxford,

他在牛津的拉德克利夫醫院接受治療，

and fortunately for him,

幸運的是，

a small team of doctors

由霍華德·佛洛里醫生

led by a Dr. Howard Florey

領導的一個醫療小團隊

had managed to synthesize

成功地合成了

a very small amount of penicillin,

微量的青黴素，

a drug that had been discovered

在 12 年前，由亞歷山大·佛萊明

12 years before by Alexander Fleming

所發現的一種藥物，

but had never actually been used to treat a human,

但是從來沒有在人體上使用過，

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

事實上，甚至沒人知道 這個藥是否有效，

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

如果這藥物不純淨的話會不會致死，

but Florey and his team figured

但是佛洛里和他的團隊覺得

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

如果他們一定要試用這個藥，

on someone who was going to die anyway.

不妨用在無藥可救的患者身上。

So they gave Albert Alexander,

於是他們將藥用在亞柏·亞歷山大

this Oxford policeman, the drug,

那位牛津警察的身上。

and within 24 hours,

在 24 小時之內，

he started getting better.

他的狀況開始好轉。

His fever went down, his appetite came back.

他的燒退了，胃口也恢復了。

Second day, he was doing much better.

第二天，他康復得更好。

They were starting to run out of penicillin,

不過青黴素就快用完，

so what they would do was run with his urine

所以醫生們採集他的尿液

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

從尿液裡重新合成青黴素，

and give it back to him,

再用來治療他，

and that worked.

這個方法也可行。

Day four, well on the way to recovery.

第四天，他仍在慢慢康復。

This was a miracle.

在當時這是一個奇蹟。

Day five, they ran out of penicillin,

第五天，青黴素用完了，

and the poor man died.

那位可憐的警察就這樣去世了。

So that story didn't end that well,

這個故事的結局不太好，

but fortunately for millions of other people,

不過，在他之後，有百萬人受益，

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

就像是 40 年代初期，

who was again dying of a sepsis,

在敗血症下垂死掙扎的這個孩子，

and within just six days, you can see,

你們可以看到，在六天之內，

recovered thanks to this wonder drug, penicillin.

因為神奇的青黴素，這孩子痊癒了。

Millions have lived,

上百萬的人因它活了下來，

and global health has been transformed.

全人類的健康發生了轉變。

Now, antibiotics have been used

現在，抗生素用來

for patients like this,

治療這類病人，

but they've also been used rather frivolously

但是它們也被輕易用在

in some instances,

別的情況下，

for treating someone with just a cold or the flu,

比如說用來治療感冒和流感，

which they might not have responded to an antibiotic,

抗生素的治療效果不會很明顯。

and they've also been used in large quantities

它們也被大量地使用在 非醫療場合裡，

sub-therapeutically, which means in small concentrations,

用低濃度的抗生素，

to make chicken and hogs grow faster.

讓雞和豬長得更快一些。

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

只是為了省一些的買肉的錢，

we've spent a lot of antibiotics on animals,

我們在動物身上用很多的抗生素，

not for treatment, not for sick animals,

不是為了醫治生病的動物，

but primarily for growth promotion.

主要是為了加速生長，

Now, what did that lead us to?

這會導致什麼結果呢？

Basically, the massive use of antibiotics

在全球

大量地使用抗生素，

around the world

has imposed such large selection pressure on bacteria

促進了細菌適者生存的自然選擇，

that resistance is now a problem,

現在細菌的抗藥性成了問題，

because we've now selected for just

因為只有抗藥性強的細菌

the resistant bacteria.

才能生存到現在。

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

我敢肯定你們都在報紙上 看過類似報導，

you've seen this in every magazine

你們瀏覽的每一本雜誌

that you come across,

都有看過類似文章，

but I really want you to appreciate

但是我想讓你們明白

the significance of this problem.

這個問題的重要性。

This is serious.

這是一個很嚴重的問題。

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

下一張幻燈片展示的是 不動桿菌對碳青黴烯的抗藥性，

Acinetobacter is a nasty hospital bug,

不動桿菌是一種經常 存在於醫院的細菌，

and carbapenem is pretty much

碳青黴烯是

the strongest class of antibiotics

一種最強的抗生素

that we can throw at this bug.

用來對抗這種細菌。

And you can see in 1999

你們可以看到，在 1999 年

this is the pattern of resistance,

這是抗藥性分布圖，

mostly under about 10 percent across the United States.

在美國通常是在 10% 以下。

Now watch what happens when we play the video.

接下來隨著時間推移會發生什麼。

So I don't know where you live,

我不知道各位是住在哪裡

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

不管你住在哪裡，現在的情況

than it was in 1999,

都比 1999 年要差，

and that is the problem of antibiotic resistance.

問題所在就是對抗生素的抗藥性。

It's a global issue

這是一個全球性的問題

affecting both rich and poor countries,

富有和貧窮國家都受到了影響，

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

歸根結底，你也許會說，

isn't this really just a medical issue?

這只是一個醫學問題吧？

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

如果我們讓醫生少用抗生素，

if we taught patients how not to demand antibiotics,

讓病人不要求使用抗生素，

perhaps this really wouldn't be an issue,

不就化解難題了嘛，

and maybe the pharmaceutical companies

也許醫藥公司

should be working harder to develop

應該更努力研發

more antibiotics.

更多的抗生素。

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

但是抗生素在本質上

which makes it different from other drugs,

與其他藥物有不同的地方，

which is that if I misuse antibiotics

意味著，如果我誤用抗生素

or I use antibiotics,

或使用抗生素，

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

不僅我會受到影響， 其他人也會受到影響，

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

同理，有如我開車去上班

or take a plane to go somewhere,

或者坐飛機去別的地方，

that the costs I impose on others

我造成的污染也會影響到別人

through global climate change go everywhere,

因此造成氣候變化 其影響無所不在，

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

我卻不會考慮到我帶來的影響。

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

這就是經濟學裡所謂的公共問題，

and the problem of the commons is exactly

公共問題恰好就是

what we face in the case of antibiotics as well:

抗生素所面對的問題：

that we don't consider —

我們都不會考慮－

and we, including individuals, patients,

包括個人、病患、

hospitals, entire health systems —

醫院、整個醫療體系－

do not consider the costs that they impose on others

沒有仔細思考濫用抗生素

by the way antibiotics are actually used.

會給別人帶來什麼影響。

Now, that's a problem that's similar

這與我們所熟知的

to another area that we all know about,

另一個領域的問題很類似，

which is of fuel use and energy,

那就是燃油的使用和能源問題，

and of course energy use

當然，能源的使用問題

both depletes energy as well as

不僅消耗了大量資源

leads to local pollution and climate change.

也造成了當地環境污染和氣候變化。

And typically, in the case of energy,

特別是能源的使用，

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

有兩個解決方案。

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

一是更加有效率的使用現有的燃油，

and that's analogous to making better use

同樣的，我們可以更好的方式使用

of existing antibiotics,

現存的抗生素，

and we can do this in a number of ways

我們可以通過很多途徑來實現它

that we'll talk about in a second,

我們稍後再討論這個問題，

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

另一個選擇就是繼續開採燃油，

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

在抗生素的角度來說 就是尋找新的抗生素。

Now, these are not separate.

這不是分開的兩個選擇。

They're related, because if we invest heavily

它們是相關連的， 如果我們大量地投資

in new oil wells,

在開採新的油井，

we reduce the incentives for conservation of oil

我們對原油的節約意識也就降低了，

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

抗生素也會發生同樣的事情。

The reverse is also going to happen, which is that

相反的情況也會發生，

if we use our antibiotics appropriately,

如果我們適當使用抗生素，

we don't necessarily have to make the investments

我們就不必投資

in new drug development.

開發新的抗生素。

And if you thought that these two were entirely,

如果你認為這兩者

fully balanced between these two options,

處在完美的平衡狀態，

you might consider the fact that

那你應該知道

this is really a game that we're playing.

其實這只是我們玩的一個遊戲。

The game is really one of coevolution,

這個遊戲只是一種共同進化，

and coevolution is, in this particular picture,

如圖所示，在獵豹和羚羊之間，

between cheetahs and gazelles.

就存在著共同進化。

Cheetahs have evolved to run faster,

獵豹進化讓自己跑得更快，

because if they didn't run faster,

因為如果牠們跑得不快，

they wouldn't get any lunch.

就吃不到午飯。

Gazelles have evolved to run faster because

羚羊也進化跑得更快

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

因為如果牠們跑不快， 就會被當作午餐，

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

我們就在和細菌玩這個遊戲，

except we're not the cheetahs,

但我們不是獵豹，

we're the gazelles,

我們是羚羊，

and the bacteria would,

而細菌，

just in the course of this little talk,

就在我們說話的同時，

would have had kids and grandkids

會一代一代地繁衍，

and figured out how to be resistant

它們會想辦法抵抗抗生素，

just by selection and trial and error,

通過選擇和試誤，

trying it over and over again.

一再地嘗試。

Whereas how do we stay ahead of the bacteria?

那我們要怎麼做 才能跑在細菌的前面呢？

We have drug discovery processes,

我們有藥物研發過程，

screening molecules,

篩選分子，

we have clinical trials,

我們有臨床試驗，

and then, when we think we have a drug,

當我們認為我們研發出新的藥物時，

then we have the FDA regulatory process.

我們還要通過食品藥物管理局的審查。

And once we go through all of that,

一旦我們完成了這些程序，

then we try to stay one step ahead

我們又要再想辦法跑在

of the bacteria.

細菌的前面。

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

很明顯這不是一個 可以長期堅持的遊戲，

or one that we can win

或是只依靠發現新藥物

by simply innovating to stay ahead.

就能贏得勝利的遊戲。

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

我們需要讓共同進化的腳步慢下來，

and there are ideas that we can borrow from energy

能源問題的解決方法 我們可以引為借鏡，

that are helpful in thinking about

我們可以嫁接

how we might want to do this in the case

解決能源問題的辦法

of antibiotics as well.

來解決抗生素的問題。

Now, if you think about how we deal with

如果你們想想我們是

energy pricing, for instance,

怎麼處理能源的價格，

we consider emissions taxes,

我們會考慮污染排放稅，

which means we're imposing the costs of pollution

意味著我們讓使用能源的人

on people who actually use that energy.

出錢來解決排放的污染。

We might consider doing that for antibiotics as well,

我們可以在抗生素上做同樣的事，

and perhaps that would make sure that antibiotics

也許可以讓抗生素

actually get used appropriately.

被適當的使用。

There are clean energy subsidies,

還有清潔能源補貼，

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

鼓勵使用低污染的能源，

or perhaps don't need fossil fuels.

也許最後我們都不需要石油了。

Now, the analogy here is, perhaps we need

同樣的，或許我們必需

to move away from using antibiotics,

遠離抗生素，

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

你仔細想想，什麼可以代替抗生素？

Well, turns out that anything that reduces

一切可以減少抗生素使用的東西

the need for the antibiotic would really work,

都是可行的，

so that could include improving hospital infection control

包括提高醫院防治感染的能力，

or vaccinating people,

給人們打疫苗，

particularly against the seasonal influenza.

特別是抵抗季節性流感的疫苗。

And the seasonal flu is probably

季節性流感很可能

the biggest driver of antibiotic use,

是抗生素使用最多的地方，

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

在我國和其他國家都是，

and that could really help.

注射疫苗可以提供極大的幫助。

A third option might include something like tradeable permits.

第三種選擇包括交易許可。

And these seem like faraway scenarios,

這聽起來似乎和抗生素掛不上邊，

but if you consider the fact that we might not

但是如果我們沒有足量抗生素

have antibiotics for many people who have infections,

給被感染的人治療，

we might consider the fact that we might

我們也許可考慮

want to allocate who actually gets to use

把抗生素分配

some of these antibiotics over others,

給最需要的人，

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

但我們需要考慮臨床需要，

but also on the basis of pricing.

以及定價的基礎。

And certainly consumer education works.

當然教育消費者也可行。

Very often, people overuse antibiotics

多數時候，大家濫用抗生素

or prescribe too much without necessarily

或者醫生開了過量的抗生素，

knowing that they do so,

卻不盡然明瞭自己已濫用或過量，

and feedback mechanisms

而反饋機制讓他們知道情況

have been found to be useful,

也被證明有效，

both on energy —

不僅在能源問題上－

When you tell someone that they're using

當你告訴某人

a lot of energy during peak hour,

他們在高峰期用了很多能源，

they tend to cut back,

他們一般都會變得節約一些，

and the same sort of example has been performed

同樣的例子

even in the case of antibiotics.

在抗生素上也有所體現。

A hospital in St. Louis basically would put up

聖路易斯的一家醫院

on a chart the names of surgeons

把外科醫生的名字做成一張表，

in the ordering of how much antibiotics they'd used

依上個月用了多少抗生素

in the previous month,

來進行排名，

and this was purely an informational feedback,

這全然是一個信息反饋，

there was no shaming,

這張表沒有對醫生指責，

but essentially that provided some information back

只是提供了一些資訊

to surgeons that maybe they could rethink

這樣外科醫生可以反思

how they were using antibiotics.

自己有沒有適當使用抗生素。

Now, there's a lot that can be done

如今，在供給這方面

on the supply side as well.

也有需要改善的地方。

If you look at the price of penicillin,

如果你看看青黴素的價格，

the cost per day is about 10 cents.

一天的價格是 10 美分 （三元台幣）。

It's a fairly cheap drug.

這是非常便宜的藥。

If you take drugs that have been introduced since then —

如果你使用之後發明的藥物－

linezolid or daptomycin —

利奈唑胺或者達託黴素－

those are significantly more expensive,

是要貴得多，

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

如果你可以每天花 10 美分 使用抗生素，

the idea of paying 180 dollars per day

那麼花 180 美元使用別的藥物

seems like a lot.

看起來就貴多了。

But what is that really telling us?

這個究竟告訴了我們什麼呢？

That price is telling us

價格告訴我們

that we should no longer

我們不應該

take cheap, effective antibiotics as a given

在可見的未來裡

將使用廉價有效的抗生素視為當然，

into the foreseeable future,

and that price is a signal to us

這個價格是一個信號

that perhaps we need to be paying

也許我們應該

much more attention to conservation.

重視節用抗生素。

That price is also a signal

這個價格也給出了另一個信號

that maybe we need to start looking at other technologies,

那就是我們應該開始轉向其他的技術，

in the same way that gasoline prices are a signal

就好像汽油價格是一個信號

and an impetus, to, say,

可以說它

the development of electric cars.

刺激了電動車的發展。

Prices are important signals

價格是很重要的信號

and we need to pay attention,

我們要更重視這個訊號，

but we also need to consider the fact that

但我們也要考慮到

although these high prices seem unusual for antibiotics,

雖然高價抗生素似乎不太常見，

they're nothing compared to the price per day

和某些癌症治療藥物比起來

of some cancer drugs,

這種高價基本上可以被忽視，

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

癌症藥物可能只能拖延幾個月 或者一年的時間，

whereas antibiotics would potentially

而抗生素

save a patient's life forever.

可以徹底挽救一個病人的生命。

So this is going to involve

所以一個全新的模式變革

a whole new paradigm shift,

將會發生，

and it's also a scary shift because

這種變化也會很可怕

in many parts of this country,

因為在這個國家很多地方，

in many parts of the world,

在全球各個角落，

the idea of paying 200 dollars

每天花上 200 美元

for a day of antibiotic treatment

進行抗生素治療

is simply unimaginable.

是難以想像的。

So we need to think about that.

所以我們需要好好的想一想。

Now, there are backstop options,

現在，還有一些備案，

which is other alternative technologies

人們在研發

其他可以代替的技術。

that people are working on.

It includes bacteriophages, probiotics,

包括噬菌體、益生菌，

quorum sensing, synbiotics.

細菌群聚感應、合益素。

Now, all of these are useful avenues to pursue,

如今這些都是可以探索的途徑，

and they will become even more lucrative

當新抗生素價格不斷上漲時

when the price of new antibiotics starts going higher,

它們就會變得更有利可圖，

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

我們看到市場已經開始回應，

and the government is now considering

政府也在考慮

ways of subsidizing new antibiotics and development.

為新抗生素研發提供補貼。

But there are challenges here.

但我們正面臨挑戰。

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

問題不能只光砸錢。

What we want to be able to do

我們想做的

is invest in new antibiotics

是投資研發新的抗生素

in ways that actually encourage

但要能實際鼓勵

appropriate use and sales of those antibiotics,

這些抗生素的銷售和適當使用，

and that really is the challenge here.

這才是真正的挑戰。

Now, going back to these technologies,

現在回到技術上，

you all remember the line from that famous

你們肯定記得那部知名恐龍影片，

dinosaur film, "Nature will find a way."

侏儸紀公園裡面的一句台詞 「大自然會找到自己的出路。」

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

所以這些都不是永久的解決辦法。

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

我們需要記住，不管是什麼科技，

that nature will find some way to work around it.

大自然總會找到解決方法。

You might think, well, this is just a problem

你也許會想，這只是一個

just with antibiotics and with bacteria,

有關抗生素和細菌的問題，

but it turns out that we have the exact same

但是我們在其他領域

identical problem in many other fields as well,

也有相同的問題，

with multidrug-resistant tuberculosis,

有多重抗藥性肺結核，

which is a serious problem in India and South Africa.

在南非和印度都是一個大問題。

Thousands of patients are dying because

上千的病人面臨死亡的威脅

the second-line drugs are so expensive,

因為二線藥物太昂貴，

and in some instances, even those don't work

有的情況，二線藥物都沒有作用，

and you have XDR TB.

因為你得了廣泛抗藥性肺結核。

Viruses are becoming resistant.

病毒也變得具抗藥性。

Agricultural pests. Malaria parasites.

農業害蟲、 瘧原蟲。

Right now, much of the world depends on

現在，世界上很多地方 都依賴一種藥物

one drug, artemisinin drugs,

青蒿素藥物，

essentially to treat malaria.

它用於治療瘧疾。

Resistance to artemisinin has already emerged,

對青蒿素的抗藥性已經開始顯現，

and if this were to become widespread,

如果這種情況蔓延，

that puts at risk

會使這種目前我們在全球治療瘧疾

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

安全又有效的單一療法藥物

in a way that's currently safe and efficacious.

產生風險。

Mosquitos develop resistance.

蚊子也產生了耐藥性。

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

如果你有小孩，你應該會知道頭蝨，

and if you're from New York City,

如果你是紐約人，

I understand that the specialty there is bedbugs.

我聽說那裡的特產是臭蟲。

So those are also resistant.

這些也有了抗藥性。

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

我們還得舉個一洋之隔的 英國的例子。

Turns out that rats are also resistant to poisons.

那裡的老鼠也變得抗毒藥了。

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

這些事的共同點就是

the idea that we've had these technologies

我們有了這些技術

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

讓我們戰勝了自然 70、80 或者 100 年，

and essentially in a blink,

轉眼之間，

we have squandered our ability to control,

我們就失去了控制力，

because we have not recognized

因為我們還沒有意識到

that natural selection and evolution was going to find

自然選擇和進化

總會找到一個出路，

a way to get back,

and we need to completely rethink

我們需要全盤反思

how we're going to use

我們究竟要用什麼

measures to control biological organisms,

去控制生物體，

and rethink how we incentivize

我們需要反思

我們如何促進藥物的發展及引進，

the development, introduction,

in the case of antibiotics prescription,

比如在抗生素的處方上，

and use of these valuable resources.

及如何利用這些寶貴的資源。

And we really now need to start thinking about them

我們需要把它們

as natural resources.

當作自然資源。

And so we stand at a crossroads.

我們站在一個十字路口上。

An option is to go through that rethinking

一個選擇就是反思自己

and carefully consider incentives

謹慎地考慮所有的動機

to change how we do business.

怎麼改變我們做事的方法。

The alternative is

要不然我們就會淪落在

a world in which even a blade of grass

即便一片草葉子

is a potentially lethal weapon.

也是致命武器的世界裡。

Thank you.

謝謝。

(Applause)

（掌聲）