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

譯者: 至磊Zi Le 黃Ng 審譯者: Helen Chang

Now, many of the people watching this talk

現在，許多正聽著這場演講的人 目前為止已經打了

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

一劑、兩劑、三劑， 甚至四劑信使核糖核酸疫苗。

of a messenger RNA vaccine.

With billions of these shots now in arms.

世人已經打了數十億劑 mRNA 疫苗，

it’s clear that this new way of making vaccines

結果這種生產疫苗的新方法 顯然既非常安全，又出奇地有效。

is both remarkably safe and incredibly effective.

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

但你知道讓你安全的 不是疫苗本身嗎？

It's actually you.

是你讓自己安全。

Because the human body has amazing powers

因為人體有驚人的力量，

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

可以自己製造藥物預防和治癒疾病。

You just need to know what medicine to make.

你只須知道該製造什麼藥物，

And that's what your vaccine gave you.

而這就是疫苗所給你的：

Simply a set of instructions

僅僅是一套指令，

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

關於如何保護自己、對抗新冠病毒。

Now vaccines are only the beginning.

新的疫苗只不過是個開始，

As I said before, the advent of mRNA vaccines

就像我之前所說的，

mRNA 疫苗的出現預示著 藥物的全新時代的開始。

is heralding in an entirely new era of medicines.

mRNAs give us the ability to not only prevent disease

mRNA 讓我們不只有能力預防疾病，

but also treat previously intractable disorders.

還能夠治療以前很難對付的失調。

But before I get to that,

但在討論那些之前，

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

我們先來談談這種全新的 製藥技術到底是什麼？

Well, it all comes down to proteins.

那麼，它的一切都要歸結到蛋白質。

Now, you may think of protein

你們也許把蛋白質簡單想成 某種必須攝取的東西，

as simply something that you need to eat,

an important part of your diet,

想成飲食當中重要的一環，

something that's important for you to build muscle.

想成某種對增加肌肉很重要的東西。

But it's not just muscle that contains protein.

然而不是只有肌肉含有蛋白質，

Protein makes up a huge fraction of the incredibly complicated ecosystem

它在一個極為複雜的生態系統中 占了很大一部分，

that's your entire body.

就是你的整個身體。

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

你身體的運作很像一座巨大的都市，

full of myriad buildings, interconnected buildings,

充滿無數互相連結的建築物，

with lots of different structures.

每個都有許多不同的構造。

Now, just as the word "building"

就像「建築物」這個詞語

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

無法形容大都市裡 千變萬化的建築構造，

the generic term "protein" gives no clue

「蛋白質」這個通稱也不能呈現

as to the incredible variety of molecular architectures

在分子的層級上 分子結構難以置信的多樣性。

at the molecular level.

Like buildings, proteins are not monolithic.

就像建築物一樣， 蛋白質不是千篇一律。

Our body makes many proteins.

我們的身體製造許多蛋白質：

Some, like the collagen in our skin

有些像皮膚中的膠原蛋白

that makes our skin tough but pliable.

讓我們的皮膚堅韌而有彈性；

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

有些像肌肉的肌動蛋白和肌凝蛋白 讓我們可以活動；

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

又如我們的血液富含血紅素， 運送氧氣到各個部位；

Antibodies protecting us from disease,

抗體保護我們免於疾病；

and clotting factors that close up our wounds.

凝血因子癒合我們的傷口。

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

對曾精讀生物化學教科書的人來說，

this should look familiar.

這應該要很眼熟。

This is the metabolic chart of the human body.

這是人體的代謝反應示意圖，

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

全都是體內讓你現在 可以健康活著的反應。

alive and well right now.

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

這裡每一個不同的反應都需要 一種不同的蛋白質來催化，

whose names are shown here in blue.

它們的名稱用藍字表示。

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

所以蛋白質不只構成了 你身體的一大部分，

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

也讓身體順利運作，保持健康。

Now, if we think again about buildings,

現在，如果我們再想想建築物，

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

建築物的最終構造 看起來可能很不一樣，

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

但它們全都是用一些 有限的建築材料蓋出來的，

and which of those building materials are used

而使用哪些建築材料、

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

如何規劃安排、 如何與其他材料接在一起

gives the buildings their final form.

決定了建築物最後的樣貌。

The same is true of proteins.

蛋白質也是如此：

If we zoom down to the molecular level,

如果我們放大分子層次，

we can see that proteins,

就可以看見蛋白質；

if we unravel their three-dimensional architecture,

如果我們解開蛋白質的三維結構，

are actually just long strings of building blocks.

其實就只是長鏈狀的堆砌磚而已。

And these building blocks have different shapes

這些堆砌磚有各種不同形狀，

and different propensities to interact with one another.

相互作用時也有不同的傾向。

So it's which building blocks are used

我們使用哪種堆砌磚 和它們排列成鏈狀的順序

and the order in which they are in the chain

that gives a protein is three-dimensional shape.

決定了蛋白質的三維構形。

Now here I'm only showing three proteins,

我在這裡只有展示三種蛋白質，

but creating and maintaining a healthy human

但創造、維持一個健康的人體

requires the combined action

需要超過十萬種蛋白質協同合作，

of over 100,000 different types of protein.

And our bodies make them all.

全由人體製造，

Thus our bodies are remarkable protein factories.

所以人體是非凡的蛋白質工廠。

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

在分子的層次，數字真的很驚人。

Each of the 30 trillion cells in your body --

你體內的 30 兆個細胞——

that's three with 13 zeros --

30 兆是 3 後面有 13 個零——

contains between one and 10 billion protein molecules.

每個都有 10 到 100 億個 蛋白質分子。

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

這代表你身體裡的蛋白質

as there are stars in the known universe.

跟已知的宇宙中恆星的數目一樣多。

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

你體內每種不同的細胞 會製造不同種類的蛋白質，

a different set of proteins,

不同套組的蛋白質，

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

例如我眼中正在感光的 視桿細胞和視錐細胞，

and the neurons in my brain that are interpreting that light

還有腦中正在解讀光線、 讓我看得到你們的神經細胞，

and enabling me to see you right now.

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

它們會各自製造專屬的一套蛋白質。

And like any complex building project,

就像任何複雜的建築專案，

you can imagine that the process of protein synthesis

你可以想像合成蛋白質的流程 必須受到嚴格控制，

needs to be tightly regulated

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

正確的蛋白質才會在 正確的時間和地點被製造。

But of course, with anything so complicated,

但想當然耳，這件事情這麼複雜，

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

大概也不用太意外，

偶爾會發生一次流程上的錯誤。

a fault in the algorithm.

Let's go back to that metabolic chart.

我們回去看那張代謝反應示意圖。

It’s estimated that one in 1,000 newborns

據估計每一千個新生兒中就有一個

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

無法製造圖中某一種蛋白質。

Therefore, they have lifelong complications

由於遺傳性代謝缺陷，

due to inborn metabolic errors.

他們一輩子都會有併發症。

Let's take just one of those.

我們舉其中一個為例，

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

來談談馮吉爾克病， 又稱為肝醣儲積症第一型。

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

這是因為缺乏用紅色 圈起來的這種蛋白質，

whose job it is to release stored sugars

它的功能是釋放儲存的糖分，

so that you can maintain a healthy blood sugar level

讓你在沒有進食的時候 也可以維持健康的血糖水準，

while you're fasting.

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

因此馮吉爾克病的患者不能不進食，

They must constantly eat small amounts of carbohydrates,

他們必須持續食用少量的醣類，

including getting up every one or two hours during the night

像是晚上每隔一兩個小時就要 為了吃生玉米粉食物而起床一次。

to eat raw cornstarch.

Now, imagine the toll that this takes on parents.

現在，想像這種病 對家長造成的折磨。

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

只要他們給孩子漏了一餐，

their child could slip into severe hypoglycemia,

孩子就可能陷入嚴重的 低血糖、抽搐，甚至可能死亡。

seizures and possibly death.

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

但即便這些家長可以 維持這個無盡的餵食循環，

they are plagued by lifelong complications,

他們還是終生會受到併發症的煎熬，

including delayed puberty,

包含青春期發育遲緩、 反覆感染、腎臟疾病、肝癌。

frequent infections, kidney disease and liver cancer.

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

馮吉爾克病只是一個 因缺乏蛋白質而失調的例子。

where we know what protein is missing.

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

如果能把製造缺乏的蛋白質的能力 還給那些病患會怎麼樣？

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

那我們就可以真正治癒他們的疾病， 而不是僅僅控制症狀。

And that's where mRNA comes in.

這就是 mRNA 上場的地方了，

That's also where I come in.

這也是我上場的地方：

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

我把我大半的學術生涯 用來做受好奇心所驅動的研究，

doing curiosity-based research

into the fundamental principles of how proteins are made.

深入蛋白質如何製造的基礎原則。

And my specialty was messenger RNA.

我的專長是信使核糖核酸。

Like proteins, messenger RNAs are long chainlike molecules

就像蛋白質一樣， 信使核糖核酸是長鏈狀分子，

composed of building blocks.

由堆砌磚所組成。

The four building blocks that make up messenger RNAs

構成信使核糖核酸的四種堆砌磚

form what is known as the genetic code.

形成了眾人所知的遺傳密碼。

As their name implies,

就如名稱所暗示的，

messenger RNAs carry messages:

信使核糖核酸會攜帶訊息，

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

身體轉譯來製造蛋白質的訊息。

Thus messenger RNAs are the language of life.

因此信使核糖核酸是生命的語言，

And the human body has a lot to say.

而人體有很多話要說。

So, like proteins,

跟蛋白質一樣，

your cells are chock-full of messenger RNA.

你的細胞充滿了信使核糖核酸。

Every one of your 30 trillion cells

你的 30 兆個細胞中的每一個

has hundreds of thousands of messenger RNA molecules.

都擁有數十萬個信使核糖核酸分子。

Messenger RNAs are an essential component of all living organisms.

信使核糖核酸是 所有生命體基本的組成部分，

So when you are eating protein-rich foods,

所以當你吃掉富含蛋白質的食物，

you're not only eating protein,

你不只吃了蛋白質，

you're also eating lots of messenger RNA.

也吃了很多信使核糖核酸。

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

你的身體取出食物的信使核糖核酸，

breaks it down into those component parts

把它分解成這些組成部分，

and then builds new messenger RNAs specific to your needs.

接著針對你的需求 建構新的信使核糖核酸。

Now this continual destruction and rebuilding

這種持續的分解和重建

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

是體內幾乎所有蛋白質 和信使核糖核酸都具備的特性。

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

我們舉生理時鐘為例，

This is the timer in your body

它是你體內的計時器，

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

告訴你什麼時候該清醒、 什麼時候該睡覺。

The proteins that make up this clock

構成這個時鐘的蛋白質

appear and disappear with remarkable regularity every day.

每天非常規律地出現又消失，

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

達成這種現象的方法就是

身體讓編碼那些蛋白質的 信使核糖核酸每天出現又消失。

that encode those proteins

appear and disappear every day.

Every day for your entire life,

在你一生中的每一天，天天都會得到

you get your daily dose of clock messenger RNAs

製造生理時鐘蛋白的信使核糖核酸。

producing clock proteins.

Now three properties of proper medicines

恰當的藥物應該具備三種特性：

are that their effects are of limited duration,

藥效必須有時限性，

that their effects are dose-dependent

藥效可以用劑量來控制，

and that they can be given over and over again

一次又一次的投藥 都可以產生一樣的效果。

to produce the same effect.

mRNA's are transient.

mRNA 是短期的，

The amount of protein produced

產生的蛋白質多寡 取決於有多少 mRNA ，

is dependent on how much of that mRNA is present.

And they can be induced over and over again

而且每次投藥都可以有同樣的效果。

to produce the same effect.

So wow, it seems so simple.

哇，看起來真簡單。

If we could treat a disease,

如果我們治療一種疾病，

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

如果需要某種缺乏的蛋白質 才能治療疾病，

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

我們可以簡單地給身體幾份 mRNA ，

for it to produce that protein.

讓身體製造那種蛋白質。

If that protein's only needed once,

如果那種蛋白質只需要一次，

then maybe a single dose would suffice.

也許一劑就夠了；

If a protein is needed multiple times,

如果那種蛋白質需要很多次，

then we can dose mRNA over and over again.

那我們可以反覆施打 mRNA 。

And that's exactly what's happening.

這正是現在發生的事。

So when I went on clinicaltrials.gov this morning,

我今天早上瀏覽 政府的臨床試驗網站時，

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

發現超過 175 個進行中的臨床試驗

using mRNA-based medicines

使用基於 mRNA 的藥物，

that are recruiting patients.

正在招募受試者；

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

還有 54 個臨床試驗已經就緒，

ready to be opened.

準備要開始進行。

So there is a coming tsunami of mRNA medicines.

mRNA 藥物的浪潮正在來臨。

去年，莫德納和阿斯特捷利康 在臨床試驗中回報了好的結果，

Last year, Moderna and AstraZeneca reported positive results

from a clinical trial where patients during open heart surgery

接受開心手術的病患

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

在心肌直接施打信使核糖核酸，

that told their heart muscles to grow new blood vessels

叫他們的心肌產生新的血管 以避免動脈阻塞。

in order to get around clogged arteries.

In other clinical trials we're repeatedly dosing patients

在其他臨床試驗，

我們多次施打給 遺傳性代謝缺陷患者，

with inborn metabolic errors

to treat their metabolic disease.

以治療他們的代謝疾病。

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

其中一個現正招募病患的臨床試驗 其實就是馮吉爾克病。

is for von Gierke's disease.

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

對於癌症病患， 我們正在發明個人化癌症疫苗。

These vaccines are meant to train their bodies,

這些疫苗是為了訓練 他們的身體和免疫系統攻擊癌細胞。

their immune systems, to attack their cancers.

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

這些是真正的個人化藥物， 一種疫苗專屬於一個人。

Now for personalized cancer vaccines to be the most effective,

為了讓個人化癌症疫苗 有最好的效果，

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

我們必須盡快製造出來， 回到病患的臨床測試。

We aim for a turnaround time of 45 days.

我們的目標是 45 天的工作時間。

By January of 2020,

2020 年 1 月，

we had already manufactured, quality-controlled and delivered

我們已經生產了經過品管的疫苗，

把個人化癌症疫苗 送到數十名病患手中，

to several dozen patients personalized cancer vaccines.

So we had the know-how and the capacity

所以我們有實務經驗和能力

to manufacture vaccines quickly.

快速地生產疫苗。

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

因此，當一連串新冠病毒案例

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

在 2020 年 1 月 10 日被發布到 一個公開的網頁伺服器，

we got immediately to work.

我們馬上就開始工作。

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

在兩天之內我們就與 美國國家衛生院的合作夥伴

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

針對該把哪一種棘蛋白 放在疫苗內達成共識。

Because we had done so so many times before,

因為我們已經做過很多次，

it then took our mRNA design team

我們的 mRNA 設計小組只花了一小時

just one hour to design the mRNA

就設計出 mRNA ，

that we immediately --

我們立刻……

(Applause)

（掌聲）

That we immediately put on to our manufacturing equipment.

我們立刻在製造設備上開始生產。

We were then able to make that RNA,

因此我們有能力做出 mRNA ，

get it quality-controlled,

保持品質管控，

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

在 45 天內填充、完成整隻疫苗， 送到美國國家衛生院進行臨床試驗。

Now what I find --

我覺得……

(Applause)

（掌聲）

What I find truly remarkable is that that mRNA sequence

我覺得真正驚奇的是，

我們只用一小時設計的 mRNA 序列

that took us one hour to design

is the same mRNA sequence that went into your arms,

正是你手臂注射的 相同的 mRNA 序列，

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

最後成為現在已經獲得 完全授權的 Spikevax 疫苗。

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

只花一小時設計的藥物 拯救了無數生命，

(Applause)

（掌聲）

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

每次我談到這件事 都還是覺得很不可思議。

So what does the future hold?

那麼，未來有什麼前景？

Well, I've already told you about regenerative medicine

我已經跟你們談過

再生醫學和個人化癌症疫苗了。

and personalized cancer vaccines.

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

對於癌症病患，

我們可以藉由直接 在腫瘤施打信使核糖核酸，

messenger RNA into their tumors --

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

輸入指令叫腫瘤細胞自毀，

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

或叫它們對免疫系統釋放出訊號，

beckoning the immune system to attack.

吸引免疫系統過來攻擊。

For patients with autoimmune disorders,

對於自體免疫疾病的病患，

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

我們可以輸入訊號， 抑制他們過於活躍的免疫系統。

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

我們和其他企業正在快速製造 更多的信使核糖核酸疫苗，

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

因為信使核糖核酸疫苗 可以非常快速地生產，

they're really well suited for newly emerging diseases

所以它很適合對付新出現的疾病

as well as other viruses, like the flu,

以及其他病毒，例如流感，

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

這些病毒每年都有新變種， 疫苗也需要更新。

But one of the exciting things about mRNA medicines

但 mRNA 藥物最令人振奮的特點之一

is we're not limited to sending in the instructions

是我們一次可以輸入 不只一種蛋白質的指示，

for one protein at a time.

mRNA medicines can be easily multiplexed.

所以很容易一次對抗多種病毒。

Therefore, we're working on a combination vaccine

因此，我們正在研發 一種複合式的疫苗，

for COVID, flu

對抗新冠、流感 和呼吸道融合病毒 RSV ，

and respiratory syncytial virus, or RSV:

all leading causes of hospitalization and death in the elderly.

這些病毒全都是年長者 住院、死亡的最常見原因。

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

我們希望這個疫苗成為 每年施打的加強針 ，

that you will get, just like the flu vaccine.

就像流感疫苗那樣施打。

(Applause)

（掌聲）

So finally, the very modest footprint

最後，不需要很複雜的設備

of the manufacturing equipment

就可以生產信使核糖核酸疫苗，

for making messenger RNAs

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

換言之，幾乎世界各地都可以製造。

And to take this to an extreme,

為了達成這項艱難的目標，

the American Defense Department started a program in 2019,

美國國防部在 2019 年 開始了一個專案，

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

我們與國防部合作， 將整個生產流程精簡化，

so that it can be fit into a single shipping container

讓它可以只用一個貨櫃裝載，

for rapid deployment anywhere in the world.

以便在世界各地快速部署。

So --

那麼……

(Applause)

（掌聲）

So to finish, I hope I've convinced you

那麼最後，我希望我有說服你們

that we have entered an entirely new era of medicine.

我們已經來到了藥物的全新時代。

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

學會說 mRNA 的語言、 也是生命的語言之後，

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

我們現在可以用它來製造 只針對一個人的藥物，

like a personalized cancer vaccine,

像是個人化癌症疫苗；

or can be rapidly produced and distributed to entire populations,

也可以快速生產，分配給全人類，

like the COVID-19 vaccines.

像是新冠疫苗。

And the best part?

最棒的地方是什麼？

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

最棒的地方在於我們只是 簡單地利用你自己身體的能力，

to make its own medicines.

做出你自己的藥物。

Thank you.

謝謝你們。

(Applause)

（掌聲）