How a long-forgotten virus could help us solve the antibiotics crisis | Alexander Belcredi

譯者: Lilian Chiu 審譯者: Keying Chen

Take a moment

花一點時間，

and think about a virus.

去想想病毒。

What comes to your mind?

你腦海中浮現的是什麼？

An illness?

一種疾病？

A fear?

一種恐懼？

Probably something really unpleasant.

可能是很不愉悅的東西。

And yet, viruses are not all the same.

但是，病毒並不是全都一樣。

It's true, some of them cause devastating disease.

的確，有些病毒會造成 很有破壞性的疾病。

But others can do the exact opposite -- they can cure disease.

但有些其他病毒的作用 完全相反——它們能治癒疾病。

These viruses are called "phages."

這些病毒叫做「噬菌體」。

Now, the first time I heard about phages was back in 2013.

我第一次聽到噬菌體， 是在 2013 年。

My father-in-law, who's a surgeon,

我的岳父是外科醫生，

was telling me about a woman he was treating.

他告訴我，他在治療一位女士。

The woman had a knee injury, required multiple surgeries,

這位女士有膝傷， 需要進行多個手術，

and over the course of these,

在這些手術的過程中，

developed a chronic bacterial infection in her leg.

她的腳發生了 一種慢性的細菌性感染。

Unfortunately for her,

對她來說，很不幸，

the bacteria causing the infection also did not respond

造成感染的細菌對於可取得的 抗生素藥物都沒有反應。

to any antibiotic that was available.

So at this point, typically, the only option left is to amputate the leg

所以，在這個時點，通常， 唯一的選擇就是將那條腿截肢，

to stop the infection from spreading further.

來阻止感染進一步散播。

Now, my father-in-law was desperate for a different kind of solution,

我的岳父非常希望能找到 一種不同的解決方案，

and he applied for an experimental, last-resort treatment using phages.

他申請用噬菌體的實驗性治療， 這是他能用的最後手段。

And guess what? It worked.

猜猜如何？治療見效了。

Within three weeks of applying the phages, the chronic infection had healed up,

在採用了噬菌體之後的三週內， 慢性感染就治癒了，

where before, no antibiotic was working.

之前，任何抗生素都沒有用。

I was fascinated by this weird conception:

這個怪異的概念讓我很著迷，

viruses curing an infection.

用病毒來治癒感染。

To this day, I am fascinated by the medical potential of phages.

至今，噬菌體的醫療潛力 仍然讓我著迷。

And I actually quit my job last year to build a company in this space.

去年，我真的辭掉了我的工作， 為此成立了一間公司。

Now, what is a phage?

噬菌體是什麼？

The image that you see here was taken by an electron microscope.

各位看到的影像是用 電子顯微鏡拍攝的。

And that means what we see on the screen is in reality extremely tiny.

意思就是，我們在螢幕上 看到的東西，實際上非常小。

The grainy thing in the middle with the head, the long body

中間的粒狀物有個頭， 有很長的身體，

and a number of feet --

有好幾隻腳——

this is the image of a prototypical phage.

典型的噬菌體就長這個樣子。

It's kind of cute.

還蠻可愛的。

(Laughter)

（笑聲）

Now, take a look at your hand.

看看你們的手。

In our team, we've estimated that you have more than 10 billion phages

我們的團隊估計，

在每一隻手上， 都有超過一百億個噬菌。

on each of your hands.

What are they doing there?

它們在那裡做什麼？

(Laughter)

（笑聲）

Well, viruses are good at infecting cells.

嗯，病毒很擅長感染細胞。

And phages are great at infecting bacteria.

而噬菌體則很擅長感染細菌。

And your hand, just like so much of our body,

而你們的手， 就像我們大部分的身體，

is a hotbed of bacterial activity,

是細菌活動的溫床，

making it an ideal hunting ground for phages.

對噬菌體來說， 就是打獵最理想的地方。

Because after all, phages hunt bacteria.

畢竟，細菌是噬菌體的獵物。

It's also important to know that phages are extremely selective hunters.

還要知道一件重要的事， 噬菌體是非常挑的獵人。

Typically, a phage will only infect a single bacterial species.

一般來說，一種噬菌體只會 感染一種細菌物種。

So in this rendering here, the phage that you see

所以在這張圖上，你們看到的噬菌體

hunts for a bacterium called Staphylococcus aureus,

獵取的目標是一種叫做 金黃色葡萄球菌的細菌，

which is known as MRSA in its drug-resistant form.

它的抗藥型縮寫為 MRSA。

It causes skin or wound infections.

它會造成皮膚或傷口的感染。

The way the phage hunts is with its feet.

噬菌體獵取的方式是用它的腳。

The feet are actually extremely sensitive receptors,

這些腳其實是非常敏感的接受器，

on the lookout for the right surface on a bacterial cell.

負責留心細菌細胞上 有沒有對的表面。

Once it finds it,

一旦找到對的表面， 噬菌體就會插上細菌的細胞壁，

the phage will latch on to the bacterial cell wall

and then inject its DNA.

接著注入它的 DNA。

DNA sits in the head of the phage

DNA 存在於噬菌體的頭部，

and travels into the bacteria through the long body.

透過長長的身體，傳輸到細菌中。

At this point, the phage reprograms the bacteria

此時，噬菌體就會改變 細菌的 DNA 編碼，

into producing lots of new phages.

來產生出很多新噬菌體。

The bacteria, in effect, becomes a phage factory.

實際上，細菌就變成了 噬菌體生產工廠。

Once around 50-100 phages have accumulated within the bacteria cell,

等到細菌細胞中累積有 大約 50~100 個噬菌體時，

the phages are then able to release a protein

噬菌體就能夠釋放出一種蛋白質，

that disrupts the bacteria cell wall.

導致細菌的細胞壁裂開。

As the bacteria bursts, the phages move out

當細菌爆裂開，噬菌體就會跑出來，

and go on the hunt again for a new bacteria to infect.

繼續去打獵，尋找並感染新的細菌。

Now, I'm sorry, this probably sounded like a scary virus again.

對不起，這可能聽起來 又像是駭人的病毒。

But it's exactly this ability of phages --

但正是噬菌體的這種能力——

to multiply within the bacteria and then kill them --

在細菌裡面繁殖並殺死細菌——

that make them so interesting from a medical point of view.

讓噬菌體從醫學的觀點 來看十分有趣。

The other part that I find extremely interesting

還有另一部分， 我也覺得非常有趣，

is the scale at which this is going on.

就是這個現象發生的規模。

Now, just five years ago, I really had no clue about phages.

五年前，我對噬菌體一無所知。

And yet, today I would tell you they are part of a natural principle.

但，現今，我會告訴各位， 它們是自然法則的一部分。

Phages and bacteria go back to the earliest days of evolution.

噬菌體和細菌可以 追溯回演化的最早期。

They have always existed in tandem, keeping each other in check.

它們一直一前一後地存在， 彼此相互制衡。

So this is really the story of yin and yang, of the hunter and the prey,

所以，這其實是一個陰和陽、

獵人和獵物的顯微級故事。

at a microscopic level.

Some scientists have even estimated

有些科學家甚至估計，

that phages are the most abundant organism on our planet.

噬菌體是地球上最大量的有機體。

So even before we continue talking about their medical potential,

所以，在我們繼續談 它們的醫療潛力之前，

I think everybody should know about phages and their role on earth:

我想大家應該要了解一下噬菌體 及它們在地球上的角色：

they hunt, infect and kill bacteria.

它們會獵取、感染，並殺死細菌。

Now, how come we have something that works so well in nature,

為什麼在大自然中 我們每天身邊都有著

every day, everywhere around us,

運作得這麼好的法則，

and yet, in most parts of the world,

但在世界上大部分的地方，

we do not have a single drug on the market

市場上都沒有任何藥物

that uses this principle to combat bacterial infections?

使用這項法則來對抗細菌感染？

The simple answer is: no one has developed this kind of a drug yet,

答案很簡單： 還沒有人開發出這種藥物，

at least not one that conforms to the Western regulatory standards

至少沒有發明出符合 西方法規標準的藥物，

that set the norm for so much of the world.

畢竟西方標準是世界主要的基準。

To understand why, we need to move back in time.

若要了解為什麼， 我們得要回到過去。

This is a picture of Félix d'Herelle.

這位是費里斯·代列爾。

He is one of the two scientists credited with discovering phages.

他是發現噬菌體的兩位科學家之一。

Except, when he discovered them back in 1917, he had no clue

不過，當他在 1917 年 發現噬菌體時，

他完全不知道他發現了什麼。

what he had discovered.

He was interested in a disease called bacillary dysentery,

他對一種疾病很感興趣， 叫做細菌性痢疾，

which is a bacterial infection that causes severe diarrhea,

它是一種細菌感染， 會造成嚴重腹瀉，

and back then, was actually killing a lot of people,

那時造成了很多死亡。

因為，畢竟還沒有發明出 能治癒細菌感染的解藥。

because after all, no cure for bacterial infections had been invented.

He was looking at samples from patients who had survived this illness.

他檢視的樣本來自得過這種疾病 但存活下來的病人。

And he found that something weird was going on.

他發現有很奇怪的現象發生。

Something in the sample was killing the bacteria

在樣本中有某樣東西在殺死

that were supposed to cause the disease.

造成疾病的那些細菌。

To find out what was going on, he did an ingenious experiment.

為了了解發生了什麼事， 他做了一項很聰明的實驗。

He took the sample, filtered it

他把樣本拿來過濾，

until he was sure that only something very small could have remained,

直到他能確保留下來的東西 都是非常小的東西，

and then took a tiny drop and added it to freshly cultivated bacteria.

接著取一小滴的樣本， 加入新鮮培養出來的細菌中。

And he observed that within a number of hours,

據他觀察，在幾小時之內，

the bacteria had been killed.

細菌都被殺死了。

He then repeated this, again filtering, taking a tiny drop,

他接著重覆這個實驗， 同樣地，過濾，再取一小滴，

adding it to the next batch of fresh bacteria.

加到下一批新鮮細菌上。

He did this in sequence 50 times,

他依序做了五十次，

always observing the same effect.

總是觀察到同樣的效果。

And at this point, he made two conclusions.

此時，他做出兩項結論。

First of all, the obvious one: yes, something was killing the bacteria,

首先，很明顯的是：是的，

有某樣東西會殺死細菌， 且就存在於那液體中。

and it was in that liquid.

The other one: it had to be biologic in nature,

另一項結論：它一定是 大自然中的生物，

because a tiny drop was sufficient to have a huge impact.

因為只要一小滴， 就足以產生很大的影響。

He called the agent he had found an "invisible microbe"

他把他發現的這種媒介稱為 「看不見的微生物」，

and gave it the name "bacteriophage,"

取名為「bacteriophage」，

which, literally translated, means "bacteria eater."

字面上直譯的意思 就是「噬菌體」。

And by the way, this is one of the most fundamental discoveries

順便一提，這是現代生物學中

of modern microbiology.

最重要的基礎發現之一。

So many modern techniques go back to our understanding of how phages work --

好多現代技術都是建立在我們對於 噬菌體運作方式的了解之上——

in genomic editing, but also in other fields.

基因編輯以及其他領域。

And just today, the Nobel Prize in chemistry was announced

今天，諾貝爾化學獎公佈了，

for two scientists who work with phages and develop drugs based on that.

得獎的兩位科學家做的是 噬菌體的研究並應用來開發藥品。

Now, back in the 1920s and 1930s,

在 1920 和 1930 年代時，

people also immediately saw the medical potential of phages.

大家也馬上就看出了 噬菌體在醫療上的潛力。

After all, albeit invisible,

畢竟，儘管看不見，

you had something that reliably was killing bacteria.

總是可以依靠它來殺死細菌。

Companies that still exist today, such as Abbott, Squibb or Lilly,

現今仍然存在的公司， 如亞培、施貴寶、禮來，

sold phage preparations.

都販售噬菌體製劑。

But the reality is, if you're starting with an invisible microbe,

但，現實是，如果你從 看不見的微生物開始著手，

it's very difficult to get to a reliable drug.

要做出可靠的藥品是很困難的。

Just imagine going to the FDA today

想像一下就知道了， 現今如果要去食品及藥物管理局，

and telling them all about that invisible virus

告訴他們你想要給病人 用一種看不見的病毒。

you want to give to patients.

So when chemical antibiotics emerged in the 1940s,

所以，在 1940 年代， 當化學抗生素出現時，

they completely changed the game.

它們完全改變了這個遊戲。

And this guy played a major role.

這個傢伙扮演了重要的角色。

This is Alexander Fleming.

他是亞歷山大弗萊明， 得過諾貝爾醫學獎，

He won the Nobel Prize in medicine

for his work contributing to the development

他因為開發出最早的抗生素 盤尼西林而得獎。

of the first antibiotic, penicillin.

And antibiotics really work very differently than phages.

抗生素的運作方式和噬菌體差很多。

For the most part, they inhibit the growth of the bacteria,

大多數的情況下， 抗生素是抑制細菌的成長，

and they don't care so much which kind of bacteria are present.

它們並不太在乎 出現的細菌是哪一種細菌。

The ones that we call broad-spectrum

有一種抗生素叫做廣效抗生素，

will even work against a whole bunch of bacteria out there.

它甚至會對抗一大堆細菌。

Compare that to phages, which work extremely narrowly

相較之下，噬菌體只會針對 一種細菌物種，作用範圍很狹窄，

against one bacterial species,

and you can see the obvious advantage.

它的優勢十分明顯。

Now, back then, this must have felt like a dream come true.

在當時，感覺大概 就像是夢想成真一樣。

You had a patient with a suspected bacterial infection,

你的病人有疑似細菌感染，

you gave him the antibiotic,

你給他服用抗生素，

and without really needing to know anything else about the bacteria

對於造成疾病的那種細菌， 你並不需要知道任何資訊，

causing the disease,

many of the patients recovered.

許多病人復元了。

And so as we developed more and more antibiotics,

隨著我們開發出越來越多的抗生素，

they, rightly so, became the first-line therapy for bacterial infections.

它們很理所當然地成為了 對抗細菌感染的第一線治療。

And by the way, they have contributed tremendously to our life expectancy.

順便一提，對於我們的壽命延長， 它們也有極大的貢獻。

We are only able to do complex medical interventions

我們現今能夠做到複雜的 醫療干預以及醫療手術，

and medical surgeries today

because we have antibiotics,

都是因為我們有抗生素， 不用再擔心病人

and we don't risk the patient dying the very next day

在手術過程中受到 細菌感染，導致隔天死亡。

from the bacterial infection that he might contract during the operation.

So we started to forget about phages, especially in Western medicine.

所以，我們開始忘卻了噬菌體， 特別是在西藥的領域中。

And to a certain extent, even when I was growing up, the notion was:

而且忘卻程度已經到了， 我成長過程中聽到的觀念是：

we have solved bacterial infections; we have antibiotics.

我們已經解決了細菌感染， 我們有抗生素。

Of course, today, we know that this is wrong.

當然，現今我們知道這是錯的。

Today, most of you will have heard about superbugs.

現今，大部分人都聽過超級細菌。

Those are bacteria that have become resistant

這些細菌變成已經能夠抵抗

to many, if not all, of the antibiotics that we have developed

所有或大部分我們為了治療感染

所開發出來的抗生素。

to treat this infection.

How did we get here?

我們是怎麼走到這一步的？ 我們沒有自己想像的那麼聰明。

Well, we weren't as smart as we thought we were.

As we started using antibiotics everywhere --

當我們開始到處使用抗生素——

in hospitals, to treat and prevent; at home, for simple colds;

在醫院用來做治療和預防； 在家中用來治感冒；

on farms, to keep animals healthy --

在農場用來維持動物的健康——

the bacteria evolved.

細菌演化了。

In the onslaught of antibiotics that were all around them,

細菌到處受到抗生素的猛攻，

those bacteria survived that were best able to adapt.

存活下來的細菌是適應力最強的。

Today, we call these "multidrug-resistant bacteria."

現今，我們稱這些細菌為 「多重抗藥性細菌」。

And let me put a scary number out there.

讓我給各位看一個可怕的數字。

In a recent study commissioned by the UK government,

英國政府近期委任進行的一項研究

it was estimated that by 2050,

估計到了 2050 年，

ten million people could die every year from multidrug-resistant infections.

每年會有一千萬人因為 多重抗藥性感染而死。

Compare that to eight million deaths from cancer per year today,

現今每年死於癌症的人數 是八百萬，相比之下，

and you can see that this is a scary number.

就看得出那個數字有多可怕。

But the good news is, phages have stuck around.

但好消息是，我們還有噬菌體。

And let me tell you, they are not impressed by multidrug resistance.

讓我告訴各位，它們不覺得 多重抗藥性有什麼了不起的。

(Laughter)

（笑聲）

They are just as happily killing and hunting bacteria all around us.

它們就是很樂意獵殺掉

我們周圍的細菌。

And they've also stayed selective, which today is really a good thing.

且它們也保有選擇性， 在現今這是一件好事。

Today, we are able to reliably identify a bacterial pathogen

現今，在許多情況下， 我們可以很可靠地

辨視出造成感染的病原體。

that's causing an infection in many settings.

And their selectivity will help us avoid some of the side effects

而它們的選擇性能夠協助我們避開

廣效抗生素常見的一些副作用。

that are commonly associated with broad-spectrum antibiotics.

But maybe the best news of all is: they are no longer an invisible microbe.

但，也許最好的消息是： 它們不再是看不見的微生物。

We can look at them.

我們能夠看見它們。 我們剛剛也一起看過了。

And we did so together before.

We can sequence their DNA.

我們能夠將它們的 DNA 定序。 我們了解它們如何複製。

We understand how they replicate.

And we understand the limitations.

我們了解限制。

We are in a great place

現在我們擁有好的技術和資源來開發

to now develop strong and reliable phage-based pharmaceuticals.

強效且可靠的噬菌體藥品。

And that's what's happening around the globe.

那也是現在全球正在做的事。

More than 10 biotech companies, including our own company,

超過十間生物科技公司， 包括我們自己的公司，

都在開發人類噬菌體的應用， 來治療細菌感染。

are developing human-phage applications to treat bacterial infections.

A number of clinical trials are getting underway in Europe and the US.

在歐洲以及美國已經有許多 臨床試驗在進行中。

So I'm convinced that we're standing on the verge

所以，我深信我們已經 很接近噬菌體治療的復興。

of a renaissance of phage therapy.

And to me, the correct way to depict the phage is something like this.

對我來說，描述噬菌體的 正確方式是這樣。

(Laughter)

（笑聲）

To me, phages are the superheroes that we have been waiting for

對我來說，噬菌體是我們 一直在等待的超級英雄，

in our fight against multidrug-resistant infections.

來協助我們對抗多重抗藥性感染。

So the next time you think about a virus,

所以，下次當你想到病毒時，

keep this image in mind.

別忘了這張圖。

After all, a phage might one day save your life.

畢竟，也許有一天， 噬菌體會救你一命。

Thank you.

謝謝。

(Applause)

（掌聲）