Kathryn A. Whitehead: The tiny balls of fat that could revolutionize medicine | TED

翻译人员: Helen Chang 校对人员: Yip Yan Yeung

如果我跟你说这场疫情将会 拯救无数人的性命，你相信吗？

What if I told you that the pandemic will save the lives of millions of people?

这很难想象，

鉴于我们已经失去了 这么多挚爱之人。

但是，在人类历史进程中，

It's a difficult thing to consider,

大范围的公共卫生危机

given how many loved ones we've already lost.

是推动医疗保健和科技创新的契机。

But throughout the course of human history,

比如，黑死病使得 古腾堡印刷机得以流行，

massive public health crises

have resulted in innovation in health care and technology.

1918 年的大流感 推动了现代疫苗技术的发展。

For example, the Black Death gave rise to the Gutenberg press

新冠疫情亦如是。

and the 1918 flu pandemic led to modern vaccine technology.

以疫苗为例，

通常需要多年才能研发出来，

The COVID-19 pandemic has and will be no different.

而mRNA疫苗令人興奮地 在短短的 11 个月内就得以上市。

Just look at our vaccines --

normally developed over many years,

这怎么可能？

and the mRNA vaccines were deployed in a mind-blowing 11 months.

是因为科学家此前 已经钻研了很多年，

我们才得以在这么紧急的情况下

How is that even possible?

迅速运用mRNA技术。

It was possible because scientists have been working for many years

具体而言，

to get us to the point where we could use mRNA quickly

我们已经在mRNA如何攻克 其最大的问题上研究多年，

in an emergency situation.

这个问题就是它通常 无法抵达我们体内正确的位置。

Specifically,

we've been working on how to help mRNA with its biggest problem,

幸运的是， 我们及时解决了这个问题，

which is that it doesn't normally go to the right places inside of our bodies.

我想和大家分享 我们解决问题的这项技术。

使用mRNA时，

Fortunately, we got around that problem just in time,

它会通过肌肉注射， 进入体内循环的血液，

and I'd like to tell you about the technology that we use to do it.

但我们真正需要的是 让它进入我们的细胞中。

When mRNA is administered,

很不幸的是，mRNA非常脆弱，

it's injected into our muscles or our bloodstream,

而我们的身体会在 它没移动多远之前就摧毁它。

but we actually need it to go inside of our cells.

你可以把mRNA想象成 邮寄一只玻璃花瓶，

Unfortunately, mRNA is fragile,

and our bodies will destroy it before it goes very far.

如果没有防震膜和盒子，

它在送达之前早就碎了。

You can think of mRNA like a glass vase that you'd like to send in the mail

而且如果盒子上没有地址，

without a box and bubble wrap.

邮政服务系统根本不知道往哪儿送。

It'll break long before it's been delivered.

所以，如果我们要 把mRNA当作治疗手段，

And without an address on the box,

your postal delivery service will have no idea where to take it.

就需要人为介入。

除了防护装置， 它还需要知道往哪儿移动。

And so if we're going to use mRNA as a therapeutic,

这也就是我研究的领域。

it needs our help.

在过去五十年间， 和我一样的科学家和工程师

It needs protection, and it needs to be told where to go.

一直致力于为核酸药物创造载体，

And that's where I come in.

For over five decades, scientists and engineers like myself

如DNA和RNA。

通过试错，我们创造出了

have been creating the shipping materials for nucleic acid drugs,

可以把花瓶完好无损地 送去错误地址的载体；

like DNA and RNA.

或者地址对，但花瓶却破损的载体；

Through trial and error, we've created packages

that deliver intact vases to the wrong address;

被看门狗扯坏了的载体；

that delivered to the right address but with a broken vase;

或者从邮递员的背包 掉了出去的载体。

packages that get ripped apart by attacking dogs;

总之，我们花了很多年 才把它搞明白。

and packages that throw out the mail carrier's back.

给大家看一下这个结果，

这些我们称之为脂质纳米粒 （lipid nanoparticles）的微小脂肪球，

It's taken many years to get the science right.

请听我细细道来 它们是啥，有什么用。

Let me show you the result,

these tiny balls of fat that we call lipid nanoparticles.

首先，纳米就意味着非常非常小。

Let me tell you what they are and how they work.

想像一下一个人和地球的直径比较 是多么渺小的存在。

So first of all, "nano" just means really, really small.

同样的道理，一个纳米颗粒 和人体比起来也是非常渺小的。

Think of how small a person is compared to the diameter of the earth.

这些纳米颗粒由无数 称作脂质的脂肪分子组成。

That's how small a nanoparticle is compared to the person.

脂肪是非常优秀的包裹材料，

These nanoparticles are made up of several fatty molecules called lipids.

又好又有弹性。

有趣的是，我们的细胞 同样由脂肪包裹，

Fat is an awesome packing material --

以确保其弹性和受保护。

nice and bouncy.

Interestingly, our cells are also surrounded by fat

很多年以前，科学家们突发奇想，

创造出如同特洛伊木马 一样的脂质纳米粒。

to keep them flexible and protected.

Years ago, scientists had the idea to create lipid nanoparticles

由于在纳米颗粒中的脂质

与包裹在我们细胞表层的膜相似，

that would act like a Trojan horse.

细胞对纳米颗粒不排斥，

Because the lipids in the nanoparticle look similar

而这就是mRNA侵入细胞的时机。

to the membranes that surround our cells,

那么，在这些纳米颗粒中的脂质 到底是什么呢？

the cells are willing to bring the nanoparticle inside,

除了mRNA之外，还有四种成分，

and that's when the mRNA is released into the cell.

So what, exactly, are the lipids in these nanoparticles?

接下来我会分别告诉你。

首先，有一类叫做 磷脂（phospholipid）的脂质。

There are four ingredients in addition to the mRNA,

这是我们细胞膜的主要成分，

and I'll tell you about each one.

即脂肪壁，用来将细胞内液

First, there's a lipid called a phospholipid.

This is the primary ingredient in our cell membranes,

与其周围的其他物质分隔开来。

磷脂的顶端亲水，

which are the walls of fat that separate the insides of our cells

尾端则亲脂。

from everything that surrounds them.

Phospholipids have a head that likes water

因此，如果将一堆磷脂投入水中，

会迅速形成这一叫做双层脂膜 （lipid bilayer）的精美结构体。

and a tail that likes other fatty things.

这里（双层脂膜分子的）顶端朝内，

So when you throw a bunch of phospholipids together in water,

（面对着）细胞外部的水，

they form this beautiful structure called a lipid bilayer.

而分子中亲脂的部分聚集在中间。

Here, the heads face the inside and the outside of the cell,

在脂质纳米粒中，

磷脂也有类似的作用，

which is water,

and the fat-loving parts of the molecule hang out together in the middle.

将其他所有成分有序地整合在一起。

第二，有一种脂类叫做胆固醇。

In lipid nanoparticles,

phospholipids have a similar role

of keeping all of the other ingredients organized.

既然胆固醇的名声这么差，

Second, there's a lipid called cholesterol.

我们会想将其用于 治疗用的纳米颗粒中吗？

Why, if cholesterol has a bad reputation,

事实上，虽然血管中存在的 胆固醇对我们有害，

would we want to use it in a therapeutic nanoparticle?

它对细胞膜其实是 非常有益的。

It turns out that while cholesterol can be bad when it's in our bloodstream,

也就是因为我刚跟大家提到的磷脂，

它们互相之间疏离得很，

it's actually a really good thing for our cell membranes.

也很容易分散。

And that's because those phospholipids I just told you about,

胆固醇是种刚性分子，

they are entirely too free with themselves,

夹在其他脂类中间，

and they are prone to falling apart.

填补空隙并将其维持在一起。

Cholesterol is a stiff molecule

that wedges itself in between the other lipids

其在脂质纳米粒的作用类似。

它为纳米粒提供支撑结构，

to fill in the gaps and hold them all together.

以防止其在注射 和进入细胞之间分散。

It plays a similar role in our lipid nanoparticles.

It provides structural support so the nanoparticles don't fall apart

第三，有一类脂质叫做 可电离脂质（ionizable lipid）。

in between the injection and when they get into our cells.

这里的“可电离”指的是 当这些颗粒进入血管中，

Third, there's a lipid called an ionizable lipid.

它们会变成中性粒子， 以确保其无害。

Here, "ionizable" means that when these particles are in the bloodstream,

然后在细胞中转变成正电荷，

they're neutrally charged, which helps with their safety.

以帮助其释放mRNA。

Then they switch to a positive charge inside of our cells,

可电离脂质的特别之处 在于它们是在实验室合成的，

which helps them release the mRNA.

全世界的科学家们

为了找到那些可以 安全搭载mRNA的脂质材料

Ionizable lipids are special because they have to be made in the lab,

已经进行了成千上万次试验。

and scientists around the world

have tested tens of thousands of these materials

也正因为其在实验室合成，

它们往往是发明公司的专利。

to find ones that are good at delivering mRNA safely.

因此，比如莫德纳（Moderna），以及 与辉瑞（Pfizer）的合作公司BioNTech，

And because they're made in the lab,

they tend to be proprietary to the company that invented them.

So, for example, Moderna and BioNTech, the company that partnered with Pfizer,

两者发现了不同的可电离脂质，

这是两者的新冠疫苗 唯一的主要差异成分。

they discovered different ionizable lipids,

即便如此，两者的可电离脂质 差异并不怎么大，

and that is the only important ingredient in their COVID-19 vaccines that differ.

这一点还挺能让人放心，

因为互相独立研究的科学家们 达成了类似的解决方案，

And even then, their ionizable lipids aren't even that different,

其结果更加容易让人信服。

which is reassuring, because when independent groups of scientists

最后，还有一种成分，

是一种聚合物， 叫做聚乙二醇（polyethylene glycol）。

converge on similar solutions,

it's easier to trust the result.

我们就称其为PEG吧， 这样简单些。

Finally, one more ingredient.

PEG是一种亲水分子。

This one is a polymer called polyethylene glycol.

PEG包裹着脂质纳米粒， 把它聚集起来固定住。

So let's call it PEG. That's much easier.

你可以想象成其他三种脂质

PEG is a water-loving molecule.

是mRNA的包装盒和缓冲垫，

So it surrounds the lipid nanoparticle and it holds it all together.

而PEG是封箱带。

You can think of the other three lipids as the box and the bubble wrap

大家可能在新闻里听说了一小部分人

for the mRNA,

对疫苗有过敏反应。

and the PEG as the packing tape.

You may have heard in the news about a tiny fraction of people

这里有些PEG 导致过敏反应的证据。

that have allergic responses to the vaccine.

由于人们普遍在

There is some evidence that PEG could be contributing to these allergic reactions.

化妆品和家用产品中接触过PEG，

并且有些人已经对其产生抗体。

And that's because people are routinely exposed to PEG

in cosmetic and household products,

那为什么有些人有这种反应， 其他人却没有呢？

and some people have already developed antibodies against PEG.

事实证明是因为每个个体的 免疫系统的差异，

But why would this happen to some people and not to others?

就像有的人对乳胶过敏，

有的人对PEG过敏。

It turns out that every person's immune system is different,

记住这点很重要。

and just the same way that some people are allergic to latex,

但是，PEG作为美国食药监局 （FDA）认证的药物配方成分，

other people are allergic to PEG.

其使用的安全性 不是一天两天得来的，

It's important to keep in mind, however,

并且这对于疫苗的过敏反应 可能是由其它物质造成的。

that PEG has had a long history of safe use

as part of FDA-approved drug formulations,

为了确定这一副作用的根本原因， 需要做更深入的调查。

and these vaccine allergies could be caused by things other than PEG.

那么，让我们退一步看看 我们整个纳米粒。

More research is needed to get to the bottom of these side effects.

很美，对不对？

当这些成分很好地结合在一起时，

All right, so let's take a step back and look at our whole nanoparticle.

结果感人。

至于疫苗，

Beautiful, right?

当这些纳米粒注射进我们的肌肉，

When these ingredients all fit together nicely,

the result is a deliverywoman's dream.

它们把mRNA带入我们的细胞中。

In the case of the vaccines,

然后， mRNA作为信使，

after these nanoparticles get injected into our muscle,

通知我们的细胞 为防御外敌入侵做准备。

they take the mRNA into our cells.

在这里，就是冠状病毒纤突蛋白。

There, the mRNA acts like an instruction manual

当我们的免疫细胞 发现了纤突蛋白，

that tells our cells to make a foreign protein,

就会保护我们免受其扰，

in this case, the coronavirus spike protein.

并通过记住这些外敌，

When our immune cells see the spike protein,

在其杀回马枪时置之于死地。

they rush to protect us from it,

就在我们话语间，

mRNA疫苗一直在 抵御新冠病毒，拯救生命。

and they teach themselves to remember it,

so that they can kill it if it ever returns.

它们是我们打赢这场战役的 第一个也是最好用的武器，

As we speak,

the mRNA vaccines are out there saving lives from the coronavirus.

它们也是我们快速应对 病毒变异的最好手段，

They were our first and best tool to combat this nightmare,

因为我们不用替换 脂质纳米粒这一载体，

and they are our best hope of responding swiftly to viral variance

只需替换其内部的 mRNA即可。

because we can keep our lipid nanoparticle packaging the same,

这是最重要的一点：

对于mRNA疗法而言，

and all we have to do is swap out the mRNA that's inside.

这些疫苗仅仅是个开端。

But here's the best part:

mRNA可以被用来 治愈许多其他疾病。

for mRNA therapeutics,

these vaccines are only the beginning.

因此，在将来我们很有可能 可以治愈许多恶疾，

mRNA can be used to treat or cure many diseases.

比如囊胞性纤维症、

肌肉萎缩症、

So in the future, we will likely have treatments for many terrible diseases,

以及镰状细胞性贫血等。

这些疾病是由突变的蛋白质引起的，

including cystic fibrosis,

我们可以通过mRNA

muscular dystrophy

使细胞自行修正其蛋白质。

and sickle cell anemia.

These diseases are caused by mutated proteins,

我们能治愈乳腺癌、 血癌、肺癌等等。

and we can use mRNA to ask our cells

to make the correct version of these proteins.

我们可以使用mRNA片段 培育免疫细胞，

We'll have treatments for cancer -- breast, blood, lungs -- you name it.

寻找和杀死癌症细胞的方法。

Here, we'll use mRNA to teach our immune cells

然后，如果我们幸运的话，

我们就能研发出对抗全球 最致命的可怕病原体疫苗，

how to find and kill cancer cells.

And then, if we're lucky, we'll have vaccines

比如，疟疾、埃博拉病毒和艾滋病。

against some of the most deadly and feared pathogens across the globe,

有一些产品其实已经在临床试验，

including malaria, Ebola and HIV.

而新冠疫苗的成功

为这些疗法的未来迭代打下了基础。

Some of these products are already in clinical trials,

and the success of the COVID-19 vaccines will pave the way

这就是这次疫情 拯救成千上万人命的方法。

for future generations of these therapies.

它推动了人类历史上 最迅速的疫苗开发，

This is how the pandemic will save the lives of millions.

并实现了一种以前未经批准的、 有商机的技术形式。

It catalyzed the most rapid vaccine development in history

在绝望中，我们给了 这一技术一个机会。

and brought to life a niche, previously unapproved form of technology.

如今，我们从成千上万的人们身上

And in our desperation, we gave that technology a chance.

收集着长期安全有效的数据。

通过这些数据， 对这一技术的热忱、

Now we're collecting long-term safety and efficacy data

from hundreds of millions of people.

投资、

和信任，

And with these data, interest in the technology,

将源源不断。

funding for the technology

展望未来，

and trust in the technology

将mRNA包装运输到 正确的器官和组织这一课题

will continue to grow.

仍将是实施这一技术

Looking ahead,

the packaging and delivery of mRNA to the right organs and tissues

最重要的挑战之一。

因此我将和我的同事们一起 继续忙很长一阵。

will continue to be one of the most significant challenges

to implementing this technology.

最后，我想传递希望。

And so my colleagues and I are going to be busy for a very long time.

我们正处在一场革命的风口浪尖，

Ultimately, I'm here with a message of hope.

mRNA即将永远改变世界，

We are on the cusp of a revolution.

这一切都要多亏了 这些小小的脂肪球，

是它们将这神药带来人间。

mRNA is about to change the world forever,

谢谢。

and it's all thanks to these fatty little balls

（掌声）

that take this miracle medicine to exactly where it's needed.

Thank you.

(Applause)