The World’s Rarest Diseases — And How They Impact Everyone | Anna Greka | TED

譯者: Lilian Chiu 審譯者: Shelley Tsang 曾雯海

我想用一個故事來開始今天的演說。

I'd like to begin by telling you a story.

It's a short story about a special family.

故事很短，講的是一個特別的家庭。

In 1960, a Utah man by the name of Roscoe Nelson,

1960 年，

猶他有名男子， 名叫洛斯可‧尼爾森，

a father of six,

是六個孩子的爸爸，

died suddenly of unknown cause.

他突然因為不明原因驟逝。

He was 43 years old.

那年他四十三歲。

As a surgeon himself,

尼爾森自己是外科醫生，他知道

Dr. Nelson knew that his progressive kidney failure

他的腎功能不斷惡化， 最終一定會衰竭而致死。

would ultimately take his life.

But he was in the dark as to the cause,

但他全然不知成因為何， 也無法取得治療。

and he had no access to treatment.

Within two decades,

不到二十年，悲劇再次發生，

tragedy struck again when four of Roscoe's six children

洛斯可的六個孩子中 有四個都患上了腎衰竭。

also developed kidney failure.

Looking back as far back as the 1800s,

向前追溯到 1800 年代，

every generation in this family has been struck down at a young age

這個家庭的每一代， 都在年輕時就受到一種

神秘的惡性疾病侵害。

by a mysterious and vicious disease.

What could be the cause?

成因會是什麼？

Fast forward to 2013.

快轉到 2013 年，

A team of brilliant geneticists

一群出色的遺傳學家確定了奪走 洛斯可‧尼爾森性命的疾病的成因。

identified the cause of Roscoe Nelson's deadly disease.

It was a mutation,

成因是一種突變，

a single extra letter in the DNA,

DNA 中多了一個額外的字母，

hiding in a dark corner of a gene called MUC1.

藏在 MUC1 基因的黑暗角落中。

The mutation had been passed down from generation to generation,

這種突變由一代傳給下一代，

leading to early deaths from kidney failure.

導致因為腎衰竭造成的早逝。

The discovery of this mutation ended a decades-long diagnostic odyssey

發現這種突變，讓這個家庭 及許多其他類似的家庭十年來

for this family and many families like them.

漫長艱辛的診斷之路可以畫下句點。

Now, as a physician-scientist and cell biologist at Harvard,

身為哈佛大學的醫師科學家 和細胞生物學家，

我領悟到，研究這種疾病 以及和它類似的遺傳疾病，

I have learned that studying this disease

and genetic diseases like it

is not only important to the families they so tragically affect.

不僅僅對於不幸受到疾病 影響的家庭而言很重要，

This work is a critical scientific and research priority for all of us.

這項工作對我們所有人而言 都至關重要，是科學和研究上的

優先要務。

Why?

為什麼？

Because what my team and I uncovered by studying this seemingly obscure disease

因為我和我的團隊研究這種 看似不起眼的疾病，卻發現了

is a series of portals into the inner workings of human cells,

一系列的入口，

讓我們能一窺人類細胞的內部運作，

gaining unexpected insights into fundamental biology.

出乎意料獲得了 對於基本生物學的洞見。

And best of all, we uncovered incredible opportunities

最讚的是，

我們發現了很棒的機會，

也許可以治療不只一種 而是數十種疾病。

for the treatment of not one but many dozens of diseases.

You see, the amazing thing about science,

要知道，科學很了不起的一點，

the reason I love what I do

我熱愛我的工作的原因，

is that if you follow your curiosity,

就是：如果跟隨著你的好奇心，

it can lead to untold scientific treasures.

它可能會帶你找到未知的科學寶藏。

So in essence, my big idea for you today is ...

所以，基本上，我今天 要跟大家談的重要觀念是……

sleuthing.

偵查。

Not the kind that solves crimes,

不是偵破犯罪案件的那種偵查，

but the kind that solves scientific mysteries,

而是破解科學謎題的偵查，

what I call molecular sleuthing

我稱之為分子偵查，

or what is otherwise known as hypothesis-driven science

也有人稱之為假設驅動科學，

or curiosity-driven science.

或好奇心驅動科學。

It is an idea as old as Aristotle,

這個觀念跟亞里斯多德一樣古老，

who was born more than 2,400 years ago,

他出生的時間是至少兩千四百年前，

not far actually from where I was born and raised,

他的出生地和我出生 長大的地方並不遠：

in Thessaloniki, Greece.

希臘的塞薩洛尼基。

Aristotle taught that at the foundation of any scientific pursuit

亞里斯多德教我們， 任何科學探尋的基礎

is formulating a hypothesis,

都是制定假設，

asking a question that can be tested experimentally.

提出可以透過實驗來檢定的問題。

Sleuthing of this nature is central to the scientific method

有這種本質的偵查， 對這種科學方法相當重要，

and has led humans to amazing discoveries.

也已經引領人類完成 許多驚人的發現。

So how did molecular sleuthing help us unlock the secrets

所以，分子偵查是如何協助我們破解

of the vicious mutation that killed Roscoe Nelson?

造成洛斯可‧尼爾森死亡的 惡性突變背後的秘密？

Well, once the mutation was uncovered,

突變被發現了之後，

the next question was

下一個問題就是

how can a single extra letter in the DNA lead to so much trouble?

DNA 中的一個字母， 怎麼可能造成這麼大的麻煩？

My team and I got to work,

我和我的團隊投入研究，

using classical hypothesis-driven science,

用古典的假設驅動科學，

but with a twist.

但有做些改變。

Our molecular detective work is now supercharged

我們的分子偵查工作 現在被大大強化了，

by our ability to use modern, scalable tools and technologies.

這要歸功於我們可以使用 現代化、可擴展的工具和技術。

Let me explain.

容我解釋。

To understand how a single extra letter in the DNA can lead to disease,

要了解為什麼 DNA 中只是 多一個額外字母就會造成疾病，

I must first remind you of some basic biology.

我必須要先幫大家 複習一些基礎生物學。

In nearly every cell in our bodies,

幾乎在我們身體中的每個細胞裡，

the three billion letters of genetic information, the DNA,

三十億個字母的 基因資訊，也就是 DNA，

is transcribed into RNA

會被轉錄為 RNA，

and in turn, RNA churns out proteins,

RNA 會進而產生蛋白質，

which are the business end of what our cells use

蛋白質是細胞執行其基本功能 所用的工具的使用端，

to perform their basic functions.

在我們體內三十七兆個 細胞中，將 DNA 轉為 RNA

The engine that turns DNA to RNA to proteins

works tirelessly in each of 37 trillion cells in our bodies.

再轉為蛋白質的引擎 孜孜不倦地運作著。

So normally the MUC1 gene churns out a protein called mucin 1,

所以，正常來說，

MUC1 基因會產生 叫做 mucin 1 的蛋白質，

which goes to the surface of cells

這種蛋白質會移至細胞表面， 並在細胞周圍形成保護層。

and forms a protective blanket around them.

We hypothesized that the mutation in the MUC1 gene

我們假設，在 MUC1 基因中的突變

is generating a mucin 1 protein

產生出的 mucin 1 蛋白質 並沒有做它該做的事。

that is not doing what it is supposed to do.

How could we test this hypothesis?

我們要如何檢定這個假設？

A couple of decades ago, when I was a student,

數十年前，我還是學生時，

this type of work would have involved just a handful of petri dishes at a time.

這種研究通常會 一次用到一大堆培養皿。

This meant that in a day’s work,

這就表示，努力一整天，

I could really only test five or six different experimental conditions

我也只能測試

五、六組不同的實驗條件， 看在條件下細胞如何反應。

to see how the cells responded.

And then I had to spend several long days at the microscope,

接著我還得花數日的 時間在顯微鏡前，

taking images one by one, analyzing them one by one,

拍完一張影像再拍一張， 分析完一張影像再分析一張，

to finally make sense of the data.

才能終於在資料中找出道理。

Instead, my students at Harvard and MIT

而我在哈佛大學 及麻省理工學院的學生

have access to state-of-the-art computer-controlled

可以取得最先進的電腦控制 機器人系統和顯微鏡，

robotic systems and microscopes

and artificial intelligence-powered software, which enable them

以及運用人工智慧的軟體，

讓他們只需要一天的時間 就能分析數千張影像。

to analyze thousands of images,

all in a day's work.

As such, we can study cells grown in special dishes

因此，我們可以研究 在特殊培養皿中培養的細胞，

that allow us to test hundreds of experimental conditions at a time.

讓我們一次就可以測試 數百種實驗條件。

事實上，據我估計， 至今，我們的分子偵查

In fact, I estimate that our molecular sleuthing to date

has generated more than 50 million images

已經產生出了超過五千萬張影像，

containing information derived from more than 100 billion cells.

影像中的資訊來自至少

一千億個細胞。

That's as many cells as there are stars in the Milky Way.

這數量等同於銀河的星星數。

And in the end,

而到最後，

the vicious mutation that killed Roscoe Nelson

奪去洛斯可‧尼爾森性命的這種 惡性突變也藏不住它的奧秘了。

revealed its secrets.

Remember, we hypothesized that the mutation in the MUC-1 gene

記得嗎，我們假設 在 MUC-1 中的突變

is generating a mucin 1 protein

會產生出不務正業的 mucin 1 蛋白質。

that is not doing what it is supposed to do.

通常，mucin 1 會移動到細胞的表面，

Normally mucin 1 goes to the surface of cells.

However, we found that the mutation in the MUC-1 gene

然而，我們發現 MUC-1 中的突變

is generating a mangled, misshapen mutant protein

會產生一種扭曲、 變形的突變蛋白質，

它不會移動到細胞的表面，

that does not go to the surface of cells,

but instead accumulates inside.

而會在內部累積。

This led to a new hypothesis.

這讓我們有了新的假設：

Is the mutant protein getting trapped inside cells,

突變蛋白質是被困在細胞內嗎？ 這又是怎麼發生的？

and how does this happen?

After some more molecular sleuthing,

做了更多分子偵查之後，我們發現

we learned that the misshapen protein accumulates inside cells

變形的蛋白質會在細胞內部 累積的原因是另一個分子，

because of another molecule,

a so-called cargo receptor.

所謂的貨物受體。

Thinking they're being helpful,

這些貨物受體自以為是在幫忙，

these cargo receptors grab the mangled proteins

它們把扭曲的蛋白質抓起來丟上車，

and throw them on board

like cargo trucks carrying a growing heap of nasty trash

就像運輸卡車載著 越堆越多的骯髒垃圾，

with nowhere to go.

卻無處可去。

Unable to get rid of this toxic waste,

無法擺脫這些有害的廢棄物，

cells begin to die,

細胞便開始死亡，

leading to the progressive kidney failure that killed Roscoe Nelson.

漸漸導致造成洛斯可‧ 尼爾森死亡的腎衰竭。

Well, now that we had insight into the root cause of the problem,

既然我們已經洞察了問題的根源，

we could also look for a way to fix it.

我們就可以想辦法來解決它。

We went to work, testing thousands of chemical compounds

我們開始著手，

測試了數千種化學化合物， 涵蓋數百萬張細胞影像。

across millions of cell images.

And in the end,

最終，我們找出了一種化合物，

we identified one compound that could specifically remove the mutant protein.

它明確可以除掉突變蛋白質。

After some more molecular detective work,

又做了更多分子偵查研究 之後，我們發現，

we learned that this drug-like compound

這些就如同藥物的化合物 可以清除堆積的扭曲蛋白質，

can clear heaps of mangled proteins

by steering the cargo trucks,

因為它們可以操控 裝滿骯髒垃圾的運輸卡車，

the ones full of nasty trash,

into the lysosome,

進入到溶小體，

the cell's trash disposal and recycling facility,

也就是細胞的垃圾處理及回收設施，

where proteins get shredded into tiny pieces.

在那裡，蛋白質會被切成碎片。

The results were amazing.

結果相當驚人。

After giving the drug to mice with kidney disease for one week,

患有腎臟病的老鼠 使用這種藥物一週後，

the mutant protein had all but disappeared from these kidneys.

牠們腎臟中的突變蛋白質都消失了。

And yet our greatest insight was not our success

但，我們最重大的洞見

並非成功除去腎臟 細胞中的突變蛋白質。

in removing the mutant protein from these kidney cells.

We realized that our curiosity-driven work

我們了解到，

我們由好奇心驅動的研究

had solved a bigger and much more important puzzle.

破解了更大、更重要許多的謎題。

This mysterious kidney disease

這種神秘的腎臟疾病

was not so strange or mysterious after all.

到頭來其實一點也不奇怪或神秘。

In fact, we learned that it belongs to a group of disorders

事實上，我們發現， 它隸屬於一類疾病，

collectively known as toxic proteinopathies.

總稱為毒性蛋白病。

You may have heard of some of them,

各位可能聽過一些這類疾病，

all terrible, incurable diseases

全都是很可怕， 無可救藥的疾病，比如

like ALS and Alzheimer's disease.

肌萎縮側索硬化症和阿茲海默症。

OK. Now you can probably guess what happened next.

現在各位可能可以 猜出接下來的發展了。

The incredibly talented scientists on my team --

我團隊中非常出色 且有才的科學家——

Here they are.

就是這些人，

They asked --

他們問了——

(Applause)

（掌聲）

Thank you. They deserve it. Thank you.

謝謝。他們值得這些掌聲。謝謝。

They asked the next logical question.

他們依邏輯問了下一個問題。

What if these cargo receptors,

如果這些貨物受體，

what if they grab and accumulate misshapen proteins

如果它們去抓取身體中其他細胞 和器官中累積的變形蛋白質呢？

in different cells and organs in the body?

What about the eye, for example?

比如，眼睛呢？

Their curiosity paid off

他們的好奇心有了回報，

because we are now learning that this newly uncovered biology

因為我們現在發現， 這種新發現的生物學

is operative in a form of blindness called retinitis pigmentosa,

會以一種視覺障礙的形式 （視網膜色素性覆蓋症）運作，

which is caused by a different misshapen protein

這種病症就是由在眼睛細胞中 累積的另一種變形蛋白質造成。

accumulating in cells in the eye.

In preliminary studies shown here at TED for the first time,

這些初步研究在 TED 這裡是初次公開，

here is a mouse I cleared of mutant protein.

我幫這隻老鼠清除了突變蛋白質。

(Applause)

（掌聲）

And in ongoing studies, we are finding that the same may be true

我們進行中的一些研究發現， 同樣的狀況可能也出現在

for different misshapen proteins accumulating in cells in the brain,

大腦的細胞中，只是累積的 變形蛋白質是另一種，

causing some forms of Alzheimer's disease.

會造成某些形式的阿茲海默症。

In all, we estimate that more than 50 disorders

總的來說，

我們估計這種方法可以 治療超過五十種疾病。

could be amenable to this approach.

So understanding one disorder has unlocked a nodal biological mechanism

了解一種疾病

讓我們解開了一種 核心的生物學機制，

連帶得到對許多其他疾病 該如何治療的洞見，

and insights for the treatment of many more diseases

affecting surprisingly distant parts of the body,

連身體中距離很遠的部分竟然 都會受到影響，如大腦和腎臟。

like the brain and the kidney.

And so in our quest to save kidneys,

我們本來追求的是要拯救腎臟，

we are now poised to save eyes, livers, brains and more.

現在卻也準備要來拯救 眼睛、肝臟、大腦等等。

And in our efforts to save a handful of families,

我們本來努力是為了 要拯救數個家庭，

we can now save thousands more.

現在我們卻可以再拯救數千個家庭。

Just think of the possibilities.

想想這些可能性。

If our work could unlock treatments for thousands,

如果我們的研究所解鎖的 治療方法可以造福數千人，

imagine what solving the next medical mystery can do.

想像一下，解決下一個 醫學謎題能帶來什麼？

And the next one and the one after that.

還有再下一個，和再再下一個。

And remember,

別忘了，

rare genetic diseases are collectively common.

把所有罕見遺傳疾病歸為 一大類來看，就變得很常見。

They affect 10 percent of all people in North America.

在北美，所有人當中 就有 10% 受這類疾病影響。

That's hundreds of millions of people all around the globe

在全球，就有數億人受到影響，

或者，在這間房間裡， 就有一百二十個人受到影響。

or 120 of you right here in this room.

And yet, out of 8,000 genes known to cause genetic diseases,

但是，

目前已知會造成遺傳疾病的 基因有約八千個，

we have only developed a treatment for, at best, 500 of them.

當中已經找到方法治療的， 最多只有五百個。

And this is not taking into account disorders

這還沒有納入

許多基因共謀而造成 問題的那些疾病，

in which many genes conspire to cause trouble,

like schizophrenia or cancer or heart disease.

比如精神分裂症、 癌症，或心臟疾病。

We have a lot of sleuthing to do,

我們還有很多偵查要做，

and yet this is the perfect moment

但此刻是最理想的時刻，

to harness recently developed scalable tools and technologies

可以利用最近發展出來的 可擴展工具和技術，

and take this challenge head on.

正面迎擊這個挑戰。

And mind you, patients and their families are up for the challenge, too.

請注意，病人和其家屬 也都準備好面對這挑戰了。

They're using social media to organize and raise awareness,

他們會用社群媒體來組織 並提升大家的意識，

and they are becoming our true partners on scientific journeys into the unknown.

在通往未知的科學旅程上， 他們也開始成為我們的真夥伴。

This is definitely true of the Nelsons.

尼爾森家就是如此。

They have been our partners for many years now.

至今他們已經和我們搭擋許多年了。

Here's the next generation of Nelsons.

這張照片是尼爾森家的下一代。

Our work has given them hope

我們的研究給了他們希望，

that their children and their children's children

還有他們的孩子， 以及那些孩子的孩子，

can live longer, fuller, and healthier lives.

讓他們能期盼更長壽、 更完整，且更健康的人生。

And they are proud to have ignited a sleuthing revolution.

他們很驕傲能夠點燃一場偵查革命。

From a few to more and more

從少數到越來越多，

until we have precision cures for all.

直到我們能為所有人 都找到精準治療。

Thank you.

謝謝。

(Applause)

（掌聲）