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

翻译人员: Xiaobao Gan 校对人员: Carol Wang

Take a moment

大家花一点时间，

and think about a virus.

想一想病毒（是什么）。

What comes to your mind?

你脑海里浮现的是什么呢？

An illness?

是疾病？

A fear?

还是恐惧？

Probably something really unpleasant.

多半是非常不愉快的感觉吧。

And yet, viruses are not all the same.

然而，病毒的影响并非都是负面的。

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

的确，有些病毒能引发致命疾病；

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

但另一些病毒则截然 相反——它们能治愈疾病，

These viruses are called "phages."

这类病毒被称为“噬菌体”。

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

我第一次听说噬菌体 病毒要追溯到2013年，

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

我身为外科医生的岳父

was telling me about a woman he was treating.

向我介绍了他当时的一名 女性患者的治疗情况。

The woman had a knee injury, required multiple surgeries,

该女性患者膝盖受伤， 需要进行多次手术，

and over the course of these,

在进行这些手术的过程中，

developed a chronic bacterial infection in her leg.

她的腿部出现了慢性 细菌感染的症状。

Unfortunately for her,

不幸的是，

the bacteria causing the infection also did not respond

所有当时的抗生素

对引发她感染的细菌都不起作用。

to any antibiotic that was available.

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

一般来说，在这种情况下， 唯一的选择就是截肢，

to stop the infection from spreading further.

以阻止感染进一步扩大。

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

我的岳父急需一种不同的治疗方案，

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

他请求实施尚处于实验阶段的 唯一可能有效的噬菌体方案，

And guess what? It worked.

你猜怎么着？那个治疗方案生效了。

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

使用噬菌体之后不到三周， 慢性感染就得到了治愈，

where before, no antibiotic was working.

而在此之前，所有抗生素无一有效。

I was fascinated by this weird conception:

我被这个奇特的概念深深迷住了:

病毒竟然能够治愈细菌感染。

viruses curing an infection.

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

直至今日，我依然为 噬菌体的医疗潜能所着迷。

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

于是，我去年辞掉工作， 在这个领域创立了一家公司。

Now, what is a phage?

那么，究竟什么是噬菌体呢？

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

你们看到的这个影像 是用电子显微镜拍的，

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

也就是说，实际上我们在 屏幕上看到的东西极其微小。

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

中间粒状的东西有头、长长的身体、

还有很多脚——

and a number of feet --

this is the image of a prototypical phage.

这就是一个典型噬菌体的形貌，

It's kind of cute.

看上去还有点可爱呢。

(Laughter)

（笑声）

Now, take a look at your hand.

现在，看看你的手，

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

据我们团队的估计，人的每只手上

有100多亿个噬菌体。

on each of your hands.

What are they doing there?

它们在你手上干什么呢？

(Laughter)

（笑声）

Well, viruses are good at infecting cells.

事实上，病毒擅长感染细胞；

And phages are great at infecting bacteria.

而噬菌体则擅长感染细菌。

和我们的身体一样，

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

is a hotbed of bacterial activity,

你的手就是细菌活动的温床，

making it an ideal hunting ground for phages.

是噬菌体的理想狩猎场，

Because after all, phages hunt bacteria.

因为终究噬菌体会猎杀细菌。

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

还有重要的一点需要了解， 即噬菌体都是挑剔的猎手；

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

通常，一个噬菌体 只会感染一种细菌。

So in this rendering here, the phage that you see

所以，在这张渲染图中的噬菌体，

hunts for a bacterium called Staphylococcus aureus,

只会猎杀一种叫做 金黄色葡萄球菌的细菌，

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

在耐药状态下它被称为MRSA，

It causes skin or wound infections.

它会导致皮肤和伤口感染。

The way the phage hunts is with its feet.

噬菌体猎杀所用的工具是它的脚，

The feet are actually extremely sensitive receptors,

这些脚其实是超级 灵敏的感受器官，

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

用于准确探测细菌细胞的表面。

Once it finds it,

噬菌体一旦探测到细菌表面，

the phage will latch on to the bacterial cell wall

就会锁定住细菌的细胞壁，

and then inject its DNA.

接着将自己的DNA 注射进入细菌体内。

DNA sits in the head of the phage

位于噬菌体头部的DNA，

and travels into the bacteria through the long body.

通过它那长长的身躯进入细菌体内。

At this point, the phage reprograms the bacteria

这时，噬菌体会对细菌重新编码，

以生产出大量新的噬菌体。

into producing lots of new phages.

The bacteria, in effect, becomes a phage factory.

事实上，细菌已变成了噬菌体工厂。

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

一旦细菌体内积累了 约50-100个噬菌体后，

the phages are then able to release a protein

这些噬菌体就会释放

that disrupts the bacteria cell wall.

一种破坏细菌细胞壁的蛋白质。

As the bacteria bursts, the phages move out

当细菌破裂时，噬菌体就跑出来，

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

继续搜寻新的细菌进行感染。

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

很抱歉，这可能听起来 又像一种可怕的病毒了。

But it's exactly this ability of phages --

但这正是噬菌体所拥有的能力——

to multiply within the bacteria and then kill them --

在细菌内部繁殖，然后杀死细菌——

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

从医学的角度来看， 这让噬菌体显得很有趣。

The other part that I find extremely interesting

另外一个让我十分感兴趣的方面，

是这件事的发展规模。

is the scale at which this is going on.

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

就在五年前，我对噬菌体还一窍不通；

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

然而，今天我会告诉你们， 它们是自然法则的一部分。

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

噬菌体和细菌又回到了进化早期，

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

它们总是成双存在， 并且彼此相互制约；

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

这跟阴和阳，或是 猎人与猎物的关系别无二致，

at a microscopic level.

只不过它们的关系存在于微观世界。

Some scientists have even estimated

有些科学家甚至估计，

that phages are the most abundant organism on our planet.

噬菌体可能是地球上 数量最多的生命体。

So even before we continue talking about their medical potential,

所以，在我们继续讨论 它们的医疗潜能之前，

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

我想每人都该了解噬菌体， 和它们在地球上扮演的角色：

they hunt, infect and kill bacteria.

它们搜寻、感染，进而杀死细菌。

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

那么，大自然中怎么会有 如此运作完美的生物，

every day, everywhere around us,

无处不在，时时刻刻伴随着我们；

and yet, in most parts of the world,

然而在世界上大多数地方，

we do not have a single drug on the market

在我们的医药市场上，

that uses this principle to combat bacterial infections?

却没有一种能利用这种机制 去对抗细菌感染的药物呢？

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

答案其实很简单： 还没人发明这种药，

at least not one that conforms to the Western regulatory standards

至少还没有这样一种药品能够符合

that set the norm for so much of the world.

为世界多数东西制定 标准的西方监管准则，

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

想知道其中的原因， 就要往前追溯一下。

This is a picture of Félix d'Herelle.

照片中的这位是菲利克斯 · 德雷尔，

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

他是发现噬菌体的两位科学家之一。

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

只不过当1917年他发现噬菌体时，

what he had discovered.

他对于自己的发现还一无所知。

He was interested in a disease called bacillary dysentery,

当时，他对一种叫做 菌痢的疾病很感兴趣，

which is a bacterial infection that causes severe diarrhea,

这是一种由细菌感染 引发的严重腹泻疾病，

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

那个年代，这种疾病的致死率很高，

毕竟那会儿治疗细菌感染的 药物还没有问世。

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

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

当时他正在观察从疾病 幸存者身上提取的样本，

And he found that something weird was going on.

他发现了一些奇怪的事情，

Something in the sample was killing the bacteria

样本中的某种东西

正在杀死那些致病的细菌。

that were supposed to cause the disease.

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

为了查明原因，他做了 一个非常巧妙的实验。

He took the sample, filtered it

他取出样本，进行过滤，

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

直到确定样本中 只保留了极微小的生物，

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

接着，他从中取出一小滴， 滴入刚培养好的细菌中。

And he observed that within a number of hours,

他观察到，在接下来的 几个小时之内，

the bacteria had been killed.

细菌统统被杀死了。

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

于是他重复进行这个实验， 再次过滤、从中取一小滴，

adding it to the next batch of fresh bacteria.

滴入下一批最新培养出的细菌中；

He did this in sequence 50 times,

他接连将这组实验做了50次，

always observing the same effect.

每次都观察到了相同的效果。

And at this point, he made two conclusions.

于是，他得出了两个结论。

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

首先，最明显的一个结论就是： 没错，有样东西正在杀死细菌，

and it was in that liquid.

它就存在于那些液体中。

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

另外一个结论是： 它本质上一定是生物，

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

因为一小滴竟足以 产生如此大的影响。

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

他把刚发现的这种试剂 叫做“看不见的微生物”，

and gave it the name "bacteriophage,"

并将其命名为“噬菌体”，

which, literally translated, means "bacteria eater."

其字面意思就是“细菌吞噬者”。

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

顺便提一句，

这是现代微生物学上 最基础性的发现之一，

of modern microbiology.

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

许多现代科技又回到我们 对噬菌体运作机制的理解——

in genomic editing, but also in other fields.

不仅是基因编辑技术， 在其他领域也是如此。

And just today, the Nobel Prize in chemistry was announced

而就在今天，两名研究噬菌体、 并开发基于噬菌体药物的科学家

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

获得了诺贝尔化学奖。

Now, back in the 1920s and 1930s,

追溯到二十世纪 二十年代和三十年代，

people also immediately saw the medical potential of phages.

人们也立刻看到了 噬菌体的医学潜能。

After all, albeit invisible,

即使看不见噬菌体，

you had something that reliably was killing bacteria.

我们毕竟拥有了能 杀死细菌的可靠物质。

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

像雅培、百时美施贵宝或礼来 这些今天依然存在的公司，

sold phage preparations.

开始销售噬菌体制剂。

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

但问题在于，如果用一种 不可见的微生物做基础，

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

是很难生产出可靠药物的。

Just imagine going to the FDA today

试想一下，你今天就去FDA，

and telling them all about that invisible virus

向他们介绍你要给病人用的 这种不可见的病毒，

you want to give to patients.

他们会作何反应。

So when chemical antibiotics emerged in the 1940s,

所以当上世纪四十年代 化学抗生素问世的时候，

they completely changed the game.

它们彻底改变了游戏规则。

And this guy played a major role.

这主要得归功于图上的这个人。

This is Alexander Fleming.

他是亚历山大 · 弗莱明，

He won the Nobel Prize in medicine

因为他对世界上第一种抗生素

for his work contributing to the development

青霉素的开发做出了巨大贡献，

而获得了诺贝尔医学奖。

of the first antibiotic, penicillin.

And antibiotics really work very differently than phages.

抗生素与噬菌体的 作用原理截然不同。

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

最大的不同就是， 抗生素会抑制细菌生长，

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

不管是哪种细菌。

The ones that we call broad-spectrum

我们称之为广谱抗菌的抗生素，

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

它们甚至会抑制人体内所有细菌。

Compare that to phages, which work extremely narrowly

与之相比，噬菌体的 作用面则很有限，

against one bacterial species,

只对一类细菌有效，

and you can see the obvious advantage.

因此，抗生素的优势显而易见。

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

那时，抗生素的出现 让人们觉得梦想成真。

You had a patient with a suspected bacterial infection,

你有一名患者疑似患上了细菌感染，

you gave him the antibiotic,

你给他开了抗生素，

and without really needing to know anything else about the bacteria

而你不需要真正对

引发疾病的细菌有更多了解，

causing the disease,

many of the patients recovered.

很多患者的病就治好了。

And so as we developed more and more antibiotics,

因此，随着我们开发出 越来越多的抗生素，

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

新抗生素立刻就会成为 治疗细菌感染的首选。

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

顺便一提，抗生素为我们 寿命的延长做出了巨大贡献。

We are only able to do complex medical interventions

今天，我们能够进行 复杂的医疗干预

and medical surgeries today

和外科手术，

because we have antibiotics,

是因为我们有抗生素，

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

所以，我们不再冒着患者 可能因为手术中细菌感染

而在术后第二天死去的危险。

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

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

因此，我们开始忘记噬菌体的 存在，尤其是在西药中。

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

更确切的说，甚至在我 成长过程中，大家的观念都是：

we have solved bacterial infections; we have antibiotics.

我们已解决了细菌感染问题； 因为我们有了抗生素。

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

当然，今天我们都知道， 这种观念是大错特错的。

Today, most of you will have heard about superbugs.

现在，多数人都听说过超级细菌吧。

Those are bacteria that have become resistant

那是一种即便不是对所有抗生素，

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

也是对很多我们开发的、 治疗细菌感染的抗生素

to treat this infection.

有抗药性的细菌。

How did we get here?

这一切是如何发生的呢？

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

事实上，我们并非 像我们想的那样聪明。

As we started using antibiotics everywhere --

从我们开始在所有地方 都使用抗生素——

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

在医院用于治疗和预防； 在家里对付小感冒；

on farms, to keep animals healthy --

在农场用，为使动物保持健康——

the bacteria evolved.

细菌进化了。

在抗生素的围攻之下，

In the onslaught of antibiotics that were all around them,

those bacteria survived that were best able to adapt.

活下来的细菌都是适应力最强的。

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

今天，我们称之为“多药耐药性细菌”。

And let me put a scary number out there.

我要向大家展示一组可怕的数据，

In a recent study commissioned by the UK government,

在最近一项由英国 政府委托的研究中，

it was estimated that by 2050,

预计直至2050年，

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

每年大约会有一千万人 死于多药耐药性细菌感染。

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

和目前每年死于癌症的八百万人相比，

and you can see that this is a scary number.

这个数字显然非常可怕。

But the good news is, phages have stuck around.

但好消息是，噬菌体的 应用离我们不远了。

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

而且，我得告诉你们， 它们可不在乎多药耐药性。

(Laughter)

（笑声）

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

它们只是喜欢猎杀我们周围的细菌。

而且，它们仍然保持着选择性， 在今天看来依然是一件好事。

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

Today, we are able to reliably identify a bacterial pathogen

今天，我们能可靠地识别

在多种情况下造成 感染的细菌病原体，

that's causing an infection in many settings.

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

而噬菌体的选择性会帮助我们避免

通常由广谱抗生素所造成的副作用。

that are commonly associated with broad-spectrum antibiotics.

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

也许这才是最好的消息： 噬菌体不再是不可见微生物。

We can look at them.

我们可以看到它们，

And we did so together before.

之前我们已经看过了。

We can sequence their DNA.

我们能对它们的基因进行测序，

We understand how they replicate.

了解它们的复制机制。

And we understand the limitations.

我们也明白它们的局限性。

We are in a great place

我们正处在一个

to now develop strong and reliable phage-based pharmaceuticals.

能够开发强力而可靠的 基于噬菌体的药物新时代，

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

世界各地都已经开始行动了。

More than 10 biotech companies, including our own company,

包括我们公司在内， 超过10家生物科技公司

正开发人类噬菌体应用 以治疗细菌性感染，

are developing human-phage applications to treat bacterial infections.

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

数个临床试验 正在欧洲和美国进行。

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

所以，我确信我们正站在

of a renaissance of phage therapy.

噬菌体疗法复兴的边缘。

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

依我看，描画噬菌体的 正确方式应该像这样。

(Laughter)

（笑声）

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

在我看来，在与多药耐药性 细菌感染的战斗中，

in our fight against multidrug-resistant infections.

噬菌体就是我们一直 期待的超级英雄。

So the next time you think about a virus,

所以，下次你想到病毒的时候，

keep this image in mind.

请记住这个噬菌体超人形象！

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

毕竟，噬菌体也许 会在某一天挽救你的生命。

Thank you.

谢谢大家。

(Applause)

（掌声）