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

譯者: Lilian Chiu 審譯者: Helen Chang

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

如果我告訴你，

這次疫情將拯救上百萬人的 性命，你覺得如何？

It's a difficult thing to consider,

這很難想像，

given how many loved ones we've already lost.

畢竟我們已經失去了 很多我們所愛的人。

But throughout the course of human history,

但，在人類歷史上，

massive public health crises

大規模的公共衛生危機

have resulted in innovation in health care and technology.

通常會帶來健康照護 和技術上的創新。

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

以黑死病為例，

它促成了古騰堡活字印刷術，

and the 1918 flu pandemic led to modern vaccine technology.

還有 1918 年的流感大流行，

促成現代的疫苗技術。

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

新冠肺炎疫情也不會是例外。

Just look at our vaccines --

看看我們的疫苗就知道——

normally developed over many years,

通常需要多年的研發，

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

這次 mRNA 疫苗到部署出來，

令人興奮地只花了 短短十一個月的時間。

How is that even possible?

怎麽可能辦到？

It was possible because scientists have been working for many years

能辦到，是因為科學家 已經投入多年的努力，

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

讓我們已經能做到快速將 mRNA

in an emergency situation.

用在緊急情況中。

Specifically,

明確來説，

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

我們一直在研究如何解決 mRNA 最大的問題，

也就是：它一般不會抵達 我們體内正確的目的地。

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

Fortunately, we got around that problem just in time,

幸運的是，我們即時 避開了這個問題。

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

我想跟各位分享我們用在此的技術。

When mRNA is administered,

給予 mRNA 時，

it's injected into our muscles or our bloodstream,

會把它注射到我們的肌肉或血液中，

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

但我們其實需要 讓它進入我們的細胞中。

Unfortunately, mRNA is fragile,

不幸的是，mRNA 很脆弱，

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

走不了多遠就會被我們的身體消滅。

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

可以把 mRNA 想成玻璃花瓶，

你要郵寄它，

without a box and bubble wrap.

卻沒有盒子也沒有氣泡布。

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

遠在送達之前，它早已被打破了。

And without an address on the box,

而且沒有盒子上的地址，

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

郵政服務也不會知道 該把它送到哪裡去。

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

所以，如果我們要把 mRNA 用在治療上，

it needs our help.

它就需要我們的協助。

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

需要保護它，

也需要告訴它該要去哪裡。

And that's where I come in.

此時就該我出場了。

For over five decades, scientists and engineers like myself

五十年來，

像我這樣的科學家及工程師

have been creating the shipping materials for nucleic acid drugs,

一直在為核酸藥物 創造運送用的包裝材料，

like DNA and RNA.

比如 DNA 和 RNA。

Through trial and error, we've created packages

透過試誤法，

我們已經創造出一些包裹，

that deliver intact vases to the wrong address;

可以把花瓶完好地送達錯誤的地址。

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

也可以送到對的地址，但花瓶會破。

也有些包裹會被惡犬咬爛，

packages that get ripped apart by attacking dogs;

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

也有些包裹會從郵差的背包掉出來。

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

花了非常多年， 才把科學的部分做對。

Let me show you the result,

讓我給各位看看結果，

these tiny balls of fat that we call lipid nanoparticles.

這些小小的脂肪球，

我們稱為脂質奈米粒子。

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

讓我來告訴各位它們是什麼，

以及它們怎麼運作。

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

首先，

「奈米」的意思就是非常非常小。

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

想想和地球的直徑相比， 一個人有多渺小。

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

和一個人相比時， 奈米粒子也是那麼渺小。

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

這些奈米粒子是由許多叫做 「脂質」的脂肪分子組成。

Fat is an awesome packing material --

脂肪是很棒的包材——

nice and bouncy.

很好，很有彈性。

Interestingly, our cells are also surrounded by fat

有趣的是，我們的細胞 也是被脂肪包圍，

to keep them flexible and protected.

讓細胞具有彈性且受到保護。

Years ago, scientists had the idea to create lipid nanoparticles

數年前，科學家想出一個點子，

創造脂質奈米粒子，

that would act like a Trojan horse.

來當作特洛依木馬。

Because the lipids in the nanoparticle look similar

因為奈米粒子中的脂質看起來很像

to the membranes that surround our cells,

包圍我們細胞的膜，

the cells are willing to bring the nanoparticle inside,

因此細胞願意讓奈米粒子進入，

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

此時就可以把 mRNA 釋放到細胞中。

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

所以，這些奈米粒子中的 脂質到底是什麼？

There are four ingredients in addition to the mRNA,

除了 mRNA 之外，還有四種成份，

and I'll tell you about each one.

我會一個一個來談。

First, there's a lipid called a phospholipid.

首先，有一種脂質叫做磷脂。

This is the primary ingredient in our cell membranes,

它是細胞膜的主要成份，

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

細胞膜是種脂肪牆，把細胞的內部

from everything that surrounds them.

和周圍的一切分隔開來。

Phospholipids have a head that likes water

磷脂的頭部喜歡水，

and a tail that likes other fatty things.

尾部則喜歡其他有脂肪的東西。

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

所以，當你把一堆磷脂 一起丟到水中，

they form this beautiful structure called a lipid bilayer.

就會形式這種美麗的結構，

叫做磷脂雙層膜。

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

在這裡，頭部會面向 細胞的內部和外部，

which is water,

也就是水，

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

而分子中喜歡脂肪的部分，

就一起待在中間。

在脂質奈米粒子中，

In lipid nanoparticles,

phospholipids have a similar role

磷脂也扮演類似的角色，

of keeping all of the other ingredients organized.

讓所有其他成份能保持井然有序。

Second, there's a lipid called cholesterol.

再來，有一種脂質叫做膽固醇。

Why, if cholesterol has a bad reputation,

如果膽固醇的名聲這麼不好，為什麼

would we want to use it in a therapeutic nanoparticle?

我們要把它用在 治療性的奈米粒子中？

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

結果發現，雖然血液中 有膽固醇時會很不好，

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

它其實對我們的細胞膜相當好。

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

因為，我剛才談到的磷脂，

they are entirely too free with themselves,

它們自己會太過自由，

and they are prone to falling apart.

它們很容易就會散開。

Cholesterol is a stiff molecule

膽固醇是種很硬的分子，

that wedges itself in between the other lipids

會把它自己卡在其他脂質之間，

to fill in the gaps and hold them all together.

補滿空隙，讓它們能結合在一起。

It plays a similar role in our lipid nanoparticles.

它在我們的脂質奈米粒子中 也扮演類似的角色。

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

它能提供結構性的支撐，

讓奈米粒子在被注入之後，

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

進入我們的細胞之前，都不會散開。

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

第三，有一種脂質叫做離子化脂質。

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

在這裡，「離子化」的意思是

當這些粒子在血液中時，

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

屬於電中性，

這對它們的安全性有幫助。

接著，

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

在我們的細胞中， 它們會換成帶正電，

which helps them release the mRNA.

這樣能協助它們釋放 mRNA。

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

離子化脂質的特別之處在於

它們只能由實驗室製造，

and scientists around the world

而世界各地的科學家

已經測試過數萬種這類材料，

have tested tens of thousands of these materials

to find ones that are good at delivering mRNA safely.

來找出有哪些能夠 安全地遞送 mRNA。

And because they're made in the lab,

因為它們是由實驗室製造，

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

它們的所有權通常屬於 發明它們的公司。

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

所以，比如，莫德納

及 BNT，也就是和輝瑞合作的公司。

they discovered different ionizable lipids,

它們發現了不同的離子化脂質，

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

它們的新冠肺炎疫苗中

就只有這個重要成份是不同的。

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

且，儘管如此，

它們的離子化脂質也沒有非常不同，

which is reassuring, because when independent groups of scientists

這很令人寬慰，

因為當獨立的科學家團隊

converge on similar solutions,

得出的解決方案會趨向類似，

it's easier to trust the result.

就比較容易信賴這個結果。

Finally, one more ingredient.

最後，還有一種成份。

This one is a polymer called polyethylene glycol.

它是一種聚合物，

叫做聚乙二醇。

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

咱們就稱它為 PEG，比較簡單。

PEG is a water-loving molecule.

PEG 是一種很喜歡水的分子。

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

所以它會圍繞著脂質奈米粒子，

讓它不要散掉。

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

你可以把另外三種脂質想成是

mRNA 的盒子和氣泡布，

for the mRNA,

and the PEG as the packing tape.

PEG 就是打包用的膠帶。

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

你可能在新聞上看過， 有很低比例的人

that have allergic responses to the vaccine.

對疫苗會有過敏反應。

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

有一些證據顯示，PEG 可能會促成

這些過敏反應。

And that's because people are routinely exposed to PEG

那是因為人會例行性地 接觸到 PEG，

in cosmetic and household products,

在化妝品和家用產品中都有，

and some people have already developed antibodies against PEG.

有些人已經發展出 對抗 PEG 的抗體。

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

但為什麼有些人會過敏， 有些人就不會？

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

結果發現，每個人的 免疫系統都不一樣，

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

和有些人對乳類過敏同樣的道理，

other people are allergic to PEG.

也有人會對 PEG 過敏。

It's important to keep in mind, however,

不過，很重要的是要記住，

that PEG has had a long history of safe use

安全使用 PEG 的歷史已久，

as part of FDA-approved drug formulations,

它是 FDA 核准的 藥品配方的一部分。

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

而這些疫苗過敏也有可能是 PEG 以外的東西所引起。

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

還需要做更多研究才能 弄清楚這些副作用。

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

好，咱們現在退一步，

來看看整個奈米粒子。

Beautiful, right?

很美，對吧？

當這些成份通通都完美結合，

When these ingredients all fit together nicely,

the result is a deliverywoman's dream.

結果就是讓一位 送貨女子的夢想成真。

In the case of the vaccines,

就疫苗來說，

after these nanoparticles get injected into our muscle,

奈米粒子被注射進我們的肌肉之後，

they take the mRNA into our cells.

它們會把 mRNA 帶到我們的細胞裡。

There, the mRNA acts like an instruction manual

在那裡，mRNA 扮演說明書的角色，

that tells our cells to make a foreign protein,

叫我們的細胞去製造 一種外來蛋白質，

in this case, the coronavirus spike protein.

在這個例子中， 就是冠狀病毒棘蛋白。

When our immune cells see the spike protein,

當我們的免疫細胞看到了棘蛋白，

they rush to protect us from it,

它們會趕來保護我們，對抗棘蛋白，

and they teach themselves to remember it,

它們也會教自己記住這種棘蛋白，

so that they can kill it if it ever returns.

當它再次出現時，它們就能殺了它。

As we speak,

此時此刻，

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

mRNA 疫苗正在外頭

對抗冠狀病毒，拯救人命。

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

它們是我們對抗這場惡夢的 第一個武器，最好的武器，

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

它們也是我們快速因應 病毒變種的最佳希望，

because we can keep our lipid nanoparticle packaging the same,

因為我們可以繼續使用 相同的脂質奈米粒子包裹，

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

我們只要換掉裡面的 mRNA 即可。

But here's the best part:

但，最棒的是：

for mRNA therapeutics,

就 mRNA 療法來說，

these vaccines are only the beginning.

這些疫苗只是開端。

mRNA can be used to treat or cure many diseases.

mRNA 可以用來治療 或治癒許多疾病。

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

所以，在未來，

我們可能可以治療許多可怕的疾病，

including cystic fibrosis,

包括囊腫性纖維化、

muscular dystrophy

肌肉萎縮症，

and sickle cell anemia.

以及鐮刀型紅血球疾病。

These diseases are caused by mutated proteins,

造成這些疾病的是突變的蛋白質，

and we can use mRNA to ask our cells

而我們可以用 mRNA 來要求我們的細胞

to make the correct version of these proteins.

製造出這些蛋白質的正確版本。

我們將來也能治療癌症——

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

乳癌、血癌、肺癌—— 想得到的都行。

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

在這個應用上，

我們會透過 mRNA 來教我們的免疫細胞

how to find and kill cancer cells.

如何找到並殺死癌細胞。

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

接著，夠幸運的話，

我們還會有疫苗，

對抗全球各地一些

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

最致命、最讓人懼怕的病原體，

including malaria, Ebola and HIV.

包括瘧疾、伊波拉， 以及人體免疫缺損病毒。

Some of these products are already in clinical trials,

這些產品當中已經有部分 在進行臨床試驗了，

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

而新冠肺炎疫苗的成功，

也是為未來世代， 幫這些治療方式舖路。

for future generations of these therapies.

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

這就是疫情拯救 數百萬人性命的方式。

It catalyzed the most rapid vaccine development in history

它催化了史上最快速的疫苗開發，

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

催生了一個利基，

先前未被承認的技術形式。

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

在絕望之際，

我們給了那項技術一個機會。

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

現在我們在收集長期的 安全性和效力資料，

from hundreds of millions of people.

來自數億人的資料。

And with these data, interest in the technology,

有了這些資料，

對這項技術的興趣、

funding for the technology

給這項技術的資助，

and trust in the technology

以及對這項技術的信任，

will continue to grow.

都會持續增長。

Looking ahead,

至於將來，

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

包裝並遞送

mRNA 給正確的器官及組織，

will continue to be one of the most significant challenges

仍然會是導入這項技術的

to implementing this technology.

重大挑戰之一。

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

所以我和我同事將會 忙碌很長的一段時間。

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

最終，我是要帶給大家 一個希望的訊息。

We are on the cusp of a revolution.

我們正在革命的關口上。

mRNA is about to change the world forever,

mRNA 將要永遠改變世界，

全都要感謝這些小小的脂肪球，

and it's all thanks to these fatty little balls

將這種奇蹟之藥帶到需要它的地方。

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

Thank you.

謝謝。

(Applause)

（掌聲）