How mRNA Medicine Will Change the World | Melissa J. Moore | TED

翻译人员: Shuhui Huang 校对人员: Yip Yan Yeung

Now, many of the people watching this talk

在这个演讲的观众之中,

by now will have had one, two, three or even four doses

大多数一定已经接受过 一、二、三，甚至四针的

of a messenger RNA vaccine.

信使RNA疫苗了。 （mRNA: 信使核糖核酸）

With billions of these shots now in arms.

几十亿的接种量可以证明，

it’s clear that this new way of making vaccines

这种新型的疫苗制法 不仅十分安全

is both remarkably safe and incredibly effective.

还很高效。

But did you know it's not the vaccine itself that's keeping you safe?

但你知道吗， 保障你健康的并不是疫苗本身，

It's actually you.

而是你自己。

Because the human body has amazing powers

这是因为我们的人体 有着神奇的力量，

to both prevent and cure disease by making its own medicines.

可以自己制造药品 来防御并治愈疾病。

You just need to know what medicine to make.

你只要知道 所需的是什么药品，

And that's what your vaccine gave you.

你的疫苗就会给你所需——

Simply a set of instructions

一些简单的自我保护的指令，

for how to protect yourself against SARS-CoV-2.

来对抗新型冠状病毒 SARS-CoV-2。

Now vaccines are only the beginning.

但疫苗只是一个开始。

As I said before, the advent of mRNA vaccines

像我之前说的， 信使RNA疫苗的到来

is heralding in an entirely new era of medicines.

是一个药品新时代的开端。

mRNAs give us the ability to not only prevent disease

信使RNA不仅给了我们 预防疾病的能力，

but also treat previously intractable disorders.

还能治疗顽固性疾病。

But before I get to that,

但在我解释这些之前，

let's talk about what is this new way of medicines really about?

我想先聊聊这个新型疫苗 到底是个什么道理。

Well, it all comes down to proteins.

嗯，这就要聊到蛋白质了。

Now, you may think of protein

说到蛋白质，

as simply something that you need to eat,

你可能会马上想到食物，

an important part of your diet,

作为日常饮食的重要一部分，

something that's important for you to build muscle.

肌肉增长的必需品。

But it's not just muscle that contains protein.

但包含蛋白质的东西 不仅仅有肌肉。

Protein makes up a huge fraction of the incredibly complicated ecosystem

蛋白质其实是你身体， 一个相当复杂的生态系统的

that's your entire body.

重要组成部分。

In many ways, your body functions like a large city,

可以说，你的身体就像是一个大城市，

full of myriad buildings, interconnected buildings,

充满了各种盘根错节的建筑，

with lots of different structures.

有着很多不同的结构。

Now, just as the word "building"

但就像“建筑”这个词

fails to capture the incredible variety of structures that make up any large city,

很难表达出 城市的结构多样性一样，

the generic term "protein" gives no clue

“蛋白质”这个通用词

as to the incredible variety of molecular architectures

也没法解释分子结构

at the molecular level.

在分子层级的多样性。

Like buildings, proteins are not monolithic.

就像建筑， 蛋白质不是一个单一的庞大个体。

Our body makes many proteins.

我们的身体生产很多种蛋白质。

Some, like the collagen in our skin

有的蛋白质， 像我们皮肤中的胶原蛋白，

that makes our skin tough but pliable.

让我们的皮肤坚固又柔韧。

Like the actin and myosin in our muscles that enable us to move.

而肌肉中的肌动蛋白 则让我们可以行动。

Or our blood is full of hemoglobin, ferrying oxygen around.

还有我们血液中满满的血红蛋白， 则负责输送氧气。

Antibodies protecting us from disease,

免疫球蛋白（抗体） 保护我们不生病，

and clotting factors that close up our wounds.

而凝血因子则愈合伤口。

And for any of you that have ever cracked a biochemistry textbook,

如果你们有谁学过 生物化学的话，

this should look familiar.

应该对这个不陌生。

This is the metabolic chart of the human body.

这是人体的代谢图。

These are all of the reactions in your body that are keeping you

这些就是你身体中 让你现在健康活着的

alive and well right now.

一系列反应。

And each one of those reactions is catalyzed by a different protein

而每一个反应都是 由不同的蛋白质催化的，

whose names are shown here in blue.

这里蓝色字体 都是蛋白质的名字。

So proteins are not only what makes up the bulk of your body,

所以蛋白质不仅仅组成了 你身体的各个部分，

they’re also what make your body tick and keep you well.

还保证你的身体正常运行。

Now, if we think again about buildings,

所以再回到那个建筑的比喻，

the structures of buildings may look quite different in the end,

建筑的结构可能看起来形状各异，

but they're all made of a limited set of building materials

但它们都是由有限的 一系列建筑材料建成的，

and which of those building materials are used

而决定建筑最后形态的，

and how they're arranged, and how they're attached to one another

是选用的材料组合、排列方式

gives the buildings their final form.

以及如何彼此黏合。

The same is true of proteins.

蛋白质也是一样。

If we zoom down to the molecular level,

如果我们把蛋白质 放大到分子级别，

we can see that proteins,

我们可以看到，

if we unravel their three-dimensional architecture,

他们的三维结构平铺的样子，

are actually just long strings of building blocks.

就类似于长条形的积木。

And these building blocks have different shapes

这些积木有着不同的形状

and different propensities to interact with one another.

和互相发生反应的特性。

So it's which building blocks are used

所以当不同的积木组合

and the order in which they are in the chain

以不同的顺序串起来，

that gives a protein is three-dimensional shape.

就得到了立体的蛋白质。

Now here I'm only showing three proteins,

这里我只展示了三种蛋白质，

but creating and maintaining a healthy human

而构建维持一个健康的人体

requires the combined action

则需要超过十万种不同的蛋白质 共同作用。

of over 100,000 different types of protein.

And our bodies make them all.

而我们的身体可以自给自足。

Thus our bodies are remarkable protein factories.

由此可知，我们的身体 是出色的蛋白质生产工厂。

At the molecular level, the numbers are truly mind-blowing.

在分子级别看， 数据就更加惊人了。

Each of the 30 trillion cells in your body --

你身体中 30 万亿的细胞——

that's three with 13 zeros --

3 后面有 13 个 0 ——

contains between one and 10 billion protein molecules.

每个都包含了 1 到 10 万亿个蛋白质分子。

That means that you have as many protein molecules in your body

也就是说， 你身体里蛋白质分子的数量

as there are stars in the known universe.

和已知宇宙中星星的数量一样多。

Now each different cell type in your body makes a different kind of protein,

你身体中的每一种细胞， 会生产出一种不同的蛋白质，

a different set of proteins,

一套不同的蛋白质，

like the rods and cones in my eye that are detecting light right now

比如我眼睛里的杆状与锥状视觉细胞 现在正感知着光线，

and the neurons in my brain that are interpreting that light

同时我脑中的神经细胞 转化了这个光信号

and enabling me to see you right now.

才让我能看见你们。

So they make a particular set of proteins unique to it.

所以这是一套专用的蛋白质。

And like any complex building project,

就像任何复杂的建筑项目，

you can imagine that the process of protein synthesis

你能想象得出 这个蛋白质合成的过程

needs to be tightly regulated

需要有严格的规定

so that the right protein is made at the right time and in the right place.

才能让正确的蛋白质 在对的时间出现在对的地方。

But of course, with anything so complicated,

理所当然地， 这么复杂的事

it's perhaps not surprising that there's an occasional mistake,

也偶尔会出差错，

a fault in the algorithm.

精密算法中的小错误。

Let's go back to that metabolic chart.

我们再来看一下这个人体代谢图。

It’s estimated that one in 1,000 newborns

数据显示， 大约每 1000 个新生儿中，

are born without the ability to make one of the proteins on this chart.

就有一个无法制造 这图中的一种蛋白质。

Therefore, they have lifelong complications

所以这些人会因为先天的代谢差错

due to inborn metabolic errors.

而受到终生困扰。

Let's take just one of those.

让我来举一个例子——

Let's talk about von Gierke's disease or glycogen storage disease I.

冯吉尔克病（von Gierke）， 又称肝糖储存症第一型。

This is due to the lack of a protein circled here in red,

这个病是由于缺乏了 这里红圈圈出的这种蛋白质，

whose job it is to release stored sugars

这个蛋白质是负责 释放人体储存的糖分的，

so that you can maintain a healthy blood sugar level

从而让你的身体在挨饿的时候， 能保持一个健康的血糖浓度。

while you're fasting.

So von Gierke's disease patients can't fast.

也就是说， 冯吉尔克病患者不能挨饿。

They must constantly eat small amounts of carbohydrates,

他们必须不停地吃 少量的碳水化合物，

including getting up every one or two hours during the night

包括晚上睡觉的时候也要 每一到两个小时就起身

to eat raw cornstarch.

吃一些生的淀粉。

Now, imagine the toll that this takes on parents.

你可以想象 这给父母会带来多大的负担。

If they are ever to miss a feeding of their child,

只要他们有一次忘记 给孩子喂食，

their child could slip into severe hypoglycemia,

他们的孩子就会产生严重的低血糖、

seizures and possibly death.

癫痫发作甚至死亡。

But even if these patients can keep up this endless feeding cycle,

然而即使这些患者可以保证 这永无止境的进食循环，

they are plagued by lifelong complications,

他们也会终生受到并发症的困扰，

including delayed puberty,

包括青春期延迟、

frequent infections, kidney disease and liver cancer.

经常性发炎， 还有肾病和肝癌。

So von Gierke's disease is just one example of a disorder

所以冯吉尔克病是一种 我们知道缺失何种蛋白质的疾病。

where we know what protein is missing.

What if we could give those patients back the ability to make that missing protein?

那要是我们可以重塑 患者制造缺失的蛋白质的能力呢？

Then we could actually treat their disease instead of just managing their symptoms.

那我们就可以真的治愈这种疾病， 而不是仅仅控制症状。

And that's where mRNA comes in.

这就是信使RNA的用处了。

That's also where I come in.

这也是我出马的地方了。

You see, I spent the better part of my career as an academic

我的职业生涯大部分时间

都是做一个好奇心驱使的研究学者，

doing curiosity-based research

into the fundamental principles of how proteins are made.

主要研究蛋白质是如何形成的。

And my specialty was messenger RNA.

而我的主攻方向就是信使RNA。

Like proteins, messenger RNAs are long chainlike molecules

就像蛋白质， 信使RNA是由“积木”组成的

composed of building blocks.

长锁链状分子。

The four building blocks that make up messenger RNAs

组成信使RNA的四大构成要素

form what is known as the genetic code.

组成了我们所知的基因密码。

As their name implies,

就像它们的名字，

messenger RNAs carry messages:

信使RNA携带着信息：

messages that are translated by your body in order to create proteins.

是你身体所传达的 有关如何制造蛋白质的信息。

Thus messenger RNAs are the language of life.

可以说，信使RNA是生命的语言。

And the human body has a lot to say.

而人类的身体要说的可太多了。

So, like proteins,

就比如说蛋白质吧，

your cells are chock-full of messenger RNA.

你的细胞里充满着信使RNA。

Every one of your 30 trillion cells

你身体里的 30 万亿个细胞中，

has hundreds of thousands of messenger RNA molecules.

每一个都有成千上百个 信使RNA分子。

Messenger RNAs are an essential component of all living organisms.

信使RNA是 所有生物体的必备成分。

So when you are eating protein-rich foods,

所以当你在吃富含蛋白质的食物时，

you're not only eating protein,

你不仅仅在吃蛋白质，

you're also eating lots of messenger RNA.

你还在吃很多的信使RNA。

Your body takes the messenger RNA in the food that you consumed,

你的身体拿到你食物中的 信使RNA后，

breaks it down into those component parts

把它们分解

and then builds new messenger RNAs specific to your needs.

再根据你的需要 造出新的信使RNA。

Now this continual destruction and rebuilding

这个持续的拆解重建的过程

is a feature true of almost all proteins and messenger RNAs in your body.

是你身体中几乎所有 蛋白质和信使RNA自带的功能。

Let's take, for example, the circadian clock.

举个例子，生物钟。

This is the timer in your body

这是你身体里的一个闹钟，

that tells you when to be active and when to sleep.

告诉你什么时候起床 什么时候睡觉。

The proteins that make up this clock

组成这个时钟的蛋白质，

appear and disappear with remarkable regularity every day.

以一种惊人的准时性出现和消失。

The way that this is accomplished is that your body makes the messenger RNAs

这是因为 你的身体制造的信使RNA

that encode those proteins

带有使这些蛋白质

appear and disappear every day.

出现消失的信息。

Every day for your entire life,

你生命中的每一天，

you get your daily dose of clock messenger RNAs

你都会得到定量的时钟信使RNA

producing clock proteins.

生产着时钟蛋白质。

Now three properties of proper medicines

那么，对症下药的三个特征是：

are that their effects are of limited duration,

药效作用时间有限、

that their effects are dose-dependent

效果由剂量决定、

and that they can be given over and over again

和重复给药的效果不变。

to produce the same effect.

mRNA's are transient.

而信使RNA，它的效果是短暂的。

The amount of protein produced

一个信使RNA 所产生的蛋白质数量

is dependent on how much of that mRNA is present.

取决于信使RNA的量。

And they can be induced over and over again

它们也可以被多次触发

to produce the same effect.

并产生相同的效果。

So wow, it seems so simple.

噢！听起来很简单嘛。

If we could treat a disease,

如果我们想治愈一种疾病，

if there's a protein that's missing to treat a disease,

如果治愈一种疾病 需要一种蛋白质，

then we could simply give a few copies of an mRNA to the body

那么我们就可以复制几个信使RNA

for it to produce that protein.

然后放进身体来生产所需蛋白质。

If that protein's only needed once,

如果我们只需要用一次 那个蛋白质，

then maybe a single dose would suffice.

那么一剂就够了。

If a protein is needed multiple times,

如果我们需要多次使用 一种蛋白质，

then we can dose mRNA over and over again.

那么我们也可以反复注射信使RNA。

And that's exactly what's happening.

而这，就是时下正在进行的事。

So when I went on clinicaltrials.gov this morning,

所以今早当我查询 临床试验资料库（clinicaltrials.gov），

it turns out that there are over 175 clinical trials now open

上面显示现在有超过 175 个 正在进行的临床试验

using mRNA-based medicines

在使用以信使RNA为基础的药品，

that are recruiting patients.

并在招募患者。

Another 54 clinical trials are waiting in the [wings],

另外有 54 个临床试验 正蓄势待发，

ready to be opened.

随时都可以开展。

So there is a coming tsunami of mRNA medicines.

所以，信使RNA相关的药品 即将蜂拥而至。

Last year, Moderna and AstraZeneca reported positive results

去年，莫德纳和阿斯利康 在一项临床试验中的合作就有了积极效果，

from a clinical trial where patients during open heart surgery

这项试验中，研究人员 在体外循环心脏手术的过程中，

were dosed with messenger RNA injected directly into their heart muscles,

将一种刺激心肌 生成新生血管的信使RNA

that told their heart muscles to grow new blood vessels

注射到患者的心肌中，

in order to get around clogged arteries.

从而绕过堵塞的动脉。

In other clinical trials we're repeatedly dosing patients

在其他的临床试验中，

我们给有先天代谢缺陷的患者 反复注射（药品），

with inborn metabolic errors

to treat their metabolic disease.

来治疗他们的代谢疾病。

In fact, one of those clinical trials that's currently recruiting patients

事实上， 有一项正在招募患者的临床试验

is for von Gierke's disease.

就是为了治愈冯吉尔克病。

And for cancer patients, we're creating personalized cancer vaccines.

对于癌症患者， 我们也在制造定制的癌症疫苗。

These vaccines are meant to train their bodies,

这些疫苗会训练身体中的 免疫系统来攻击癌症细胞。

their immune systems, to attack their cancers.

These are truly personalized medicines, one vaccine for one person.

这些是真正定制的药品， 一人一种。

Now for personalized cancer vaccines to be the most effective,

为了让这些私人定制的癌症疫苗 发挥最大作用，

we need to get them made and back to the patient as quickly as possible.

我们需要一完成制作 就马上给患者。

We aim for a turnaround time of 45 days.

整个周期的目标时间， 是 45 天。

By January of 2020,

在 2020 年的 1 月之前，

we had already manufactured, quality-controlled and delivered

我们已经生产出了 有质量保证的癌症疫苗，

to several dozen patients personalized cancer vaccines.

并给到了几十个患者。

So we had the know-how and the capacity

所以我们不仅知道 如何制作这些疫苗，

to manufacture vaccines quickly.

也有能力快速生产。

Thus, when the sequence of the SARS-CoV-2 virus

所以 2020 年 1 月 10 日那天， 当新冠病毒 SARS-COV-2 的序列

was posted to a public web server on January 10, 2020,

在一个公共网站上公布，

we got immediately to work.

我们马上就开始了行动。

Within two days, we had agreed with our collaborators at NIH

在两天之内，我们就与 合作的国立卫生研究院 （NIH）

on exactly which form of the spike protein to put in our vaccine.

对需要在疫苗里放哪种形态的 刺突蛋白达成了共识。

Because we had done so so many times before,

因为我们之前做过太多次了，

it then took our mRNA design team

我们负责设计信使RNA的团队

just one hour to design the mRNA

只用了一个小时就设计出了 所需的信使RNA

that we immediately --

随后我们马上——

(Applause)

（鼓掌）

That we immediately put on to our manufacturing equipment.

随后我们马上就开始了生产。

We were then able to make that RNA,

45 天之内，我们生产了那种RNA、

get it quality-controlled,

进行了品质管制、

fill-finished and shipped off to NIH for the clinical trial in 45 days.

灌装、包装， 并运输到了 国立卫生研究院进行临床试验。

Now what I find --

我觉得——

(Applause)

（鼓掌）

What I find truly remarkable is that that mRNA sequence

我觉得最了不起的地方在于

that took us one hour to design

那个我们只花了一个小时设计的 信使RNA序列

is the same mRNA sequence that went into your arms,

和已全面批准并 注射进你们手臂里的

that ended up in Spikevax, our now fully approved vaccine.

莫德纳疫苗里的信使RNA序列 是同一个。

One hour to design a medicine that has saved countless lives.

一个小时就设计出来的药品 拯救了数不清的生命。

(Applause)

（鼓掌）

It still gives me goosebumps every time I talk about it.

每次我说这个的时候， 都会激动地起鸡皮疙瘩。

So what does the future hold?

所以这是怎样的未来可期？

Well, I've already told you about regenerative medicine

我已经聊过了促进细胞新生的药品

and personalized cancer vaccines.

和私人定制的癌症疫苗。

For cancer patients, we can send in -- by directly injecting

对于癌症患者，我们还可以通过 直接把信使RNA注射进

messenger RNA into their tumors --

患者的肿瘤里，

we can send in instructions telling the tumor cells to self-destruct,

来给出肿瘤自我销毁的指令，

Or having the tumor cells send out signals to the immune system,

或是让肿瘤向免疫系统

beckoning the immune system to attack.

发出进攻指令。

For patients with autoimmune disorders,

对于有自身免疫性疾病的患者，

we can send in signals that tamp down their overactive immune systems.

我们可以发送让过激的免疫系统 冷静下来的信号。

And we and others are rapidly making many more messenger RNA vaccines.

我们团队和很多其他研究者 都在快速制作更多信使RNA疫苗。

Because messenger RNA vaccines can be produced so quickly and rapidly,

因为信使RNA疫苗可以 被快速生产的特性，

they're really well suited for newly emerging diseases

它们很适合对付一些新型疾病，

as well as other viruses, like the flu,

以及像流感这种，

where new variants come out every year, and the vaccines need to be updated.

每年都会有新变种出现， 需要疫苗不断更新的病毒。

But one of the exciting things about mRNA medicines

但信使RNA疫苗的 另一激动人心之处在于，

is we're not limited to sending in the instructions

我们每次传递指令的对象， 并不限于一种蛋白质。

for one protein at a time.

mRNA medicines can be easily multiplexed.

信使RNA疫苗的复合效用 可以很容易实现。

Therefore, we're working on a combination vaccine

所以我们正在努力 实现一种复合疫苗，

for COVID, flu

来针对新冠、流感，

and respiratory syncytial virus, or RSV:

和呼吸道合胞病毒 （RSV）的组合：

all leading causes of hospitalization and death in the elderly.

都是老年群体中 住院率和致死率的首要祸首。

And we're hoping that this will then be an annual booster,

我们希望这会成为 一种一年一度的加强针，

that you will get, just like the flu vaccine.

就像每年打的流感疫苗一样。

(Applause)

（鼓掌）

So finally, the very modest footprint

最后一点，制造信使RNA所需的

of the manufacturing equipment

设备面积非常的小，

for making messenger RNAs

也就是说，

means that they can be made almost anywhere in the world.

在任何地方都可以制造它们。

And to take this to an extreme,

为了把这个优势发挥到极致，

the American Defense Department started a program in 2019,

美国国防部在 2019 年 启动了一个项目，

and we're working with them to miniaturize the entire process

与我们合作 努力把制作过程缩得更小，

so that it can be fit into a single shipping container

致力于让整个过程 可以塞进一个集装箱，

for rapid deployment anywhere in the world.

这样可以保证在世界各地 都可以快速生产。

So --

最后——

(Applause)

（鼓掌）

So to finish, I hope I've convinced you

最后，我希望我成功让你们相信了，

that we have entered an entirely new era of medicine.

我们已经进入了药品新时代。

Having learned to speak the language of mRNA, the language of life,

拥有了信使RNA的语言， 生命的语言，

we can now use it to create medicines that are just for one person,

我们可以为单独个人制造药品，

like a personalized cancer vaccine,

比如私人定制的癌症疫苗，

or can be rapidly produced and distributed to entire populations,

或是快速制造药品 并分发至全球，

like the COVID-19 vaccines.

就像新冠疫苗一样。

And the best part?

最酷的一点是什么呢？

The best part is we're simply tapping into your body's own ability

那就是，这一切只是利用了 你身体自己的能力

to make its own medicines.

来制造药品。

Thank you.

谢谢。

(Applause)

（鼓掌）