How to create a world where no one dies waiting for a transplant | Luhan Yang

譯者: Lilian Chiu 審譯者: Yanyan Hong

Hi everyone.

嗨，大家好。

I would like to introduce you to Laika.

讓我向各位介紹萊卡。

To most of us, Laika is simply a very cute pig.

對大部分的人來說， 萊卡只是一隻非常可愛的豬。

However, to hundreds of thousands of patients in need of a lifesaving organ

然而，

對於數十萬名需要器官 來救命的病人來說，

Laika is a symbol of hope.

萊卡是希望的象徵。

You see, ever since the 1970s,

在七十年代，

when organ transplants became a real option

器官移植這個選項成真了，

for patients with kidney failure and other organ diseases,

腎臟衰竭和其他器官疾病的 病人都可以選擇它，

organ supply has been an issue.

此後，器官供應便成了一個議題。

Over the last few decades,

在過去幾十年間，

the issue only worsened as organ demand has exponentially increased.

器官需求以指數增加， 使這個議題變得更糟。

Currently in the US,

目前，在美國，

there are close to 115,000 patients

有接近 11 萬 5 千名病人

in need of a lifesaving organ transplant.

需要組織移植來拯救他們的性命。

By the end of my talk,

在我的演說結束時，

one more patient will be added to this list.

就會再有一位病人加入名單中。

Today, about 100 people will get a new organ,

今天，大約有 100 人 可以得到一個新器官，

a chance to start their life anew,

一個重新開始新生活的機會，

and yet by the end of today,

但，在今天結束時，

20 others will die waiting.

會有另外 20 個人 等不到器官而死。

The situation is heartbreaking

這個情況讓人心碎，

for patients, for their families

對病人、對他們的家人，

and for the doctors who want to do more.

及對想要做更多的醫生 來說都是如此。

In some parts of the world,

在世界上的某些地方，

the situation also becomes a disturbing social issue.

這個情況也變成了 令人不安的社會議題。

In Asia, for example,

比如，在亞洲，

media outlets reported that desperate patients

媒體管道報導指出， 走投無路的病人

are obtaining organs from the cruel black market.

會從殘酷的黑市取得器官。

It is clear that a solution is needed to this crisis.

很明顯，這個危機 需要一個解決方案。

Human lives are at stake.

人命關天。

As a biologist and a geneticist,

身為生物學家和遺傳學家，

it has become my mission to help solve this problem.

協助解決這個問題成了我的使命。

Today, I am optimistic to say that we are on our way there,

今天，我能很樂觀地說， 我們正在朝那個目標邁進，

thanks to Laika.

這要感謝萊卡。

Using gene editing technology,

用基因編輯技術，

it's now possible to exquisitely create a human-transplantable organ

現在已經有可能精緻地創造出 可以移植給人類的器官，

that can be safely grown in pigs.

並讓它在安全地長在豬身上。

Before we jump into the incredible science that makes it happen,

在我們跳進去談 讓它成真的偉大科學之前，

let's have a better understanding what xenotransplantation is.

咱們先多了解一下 「異種器官移植」是什麼。

It's a process of transplanting animal organs into humans.

它是把動物組織移植到 人類身上的過程。

You may want to ask, why pig organs?

你們可能會想問， 為什麼用豬的器官？

Because some pigs carry organs with similar size and physiology

因為有些豬本身的器官

和人類器官的大小 及生理機能都很類似。

to human organs.

Over the last half a century,

在過去半個世紀，

pioneers of transplantation have tried hard to make it happen,

移植領域的先鋒 非常努力地實現這個想法，

but with limited to no success.

但成功有限，或甚至根本沒能成功。

Why is that?

為什麼會這樣？

Two fundamental hurdles stood in the way.

有兩個基本的阻礙。

First is a problem of rejection.

第一，是排斥的問題。

When our immune system sees a new organ as foreign,

當我們的免疫系統 把新器官視為是外來物，

it will reject it.

就會排斥它。

Second, and this one is specific to the organs from the pig,

第二，這是只有豬的器官 才會遇到的狀況，

every pig carries a virus that is benign to the pig,

每隻豬都帶有一種病毒， 這病毒對牠的健康有益，

but can be transmitted into humans.

但可能會被傳給人類。

It is called the porcine endogenous retrovirus (PERV),

這種病毒叫豬內源性 反轉錄病毒（PERV），

and this virus has the potential to cause a viral epidemic similar to HIV.

這種病毒有可能會造成 類似愛滋病的病毒大流行。

Without an effective way to address these issues,

因為沒有有效的方式 來處理這些議題，

the field of xenotransplantation has been on hold for more than one decade.

異種器官移植的領域 停滯了超過十年的時間。

Little progress has been made, until now.

到目前為止，進展都相當少。

Let me share with you how I got here today with Laika.

讓我分享一下，我和萊卡的故事 是怎麼今天來到這裡的。

My journey started from Emei Mountain in China.

我的旅程始於中國的峨眉山。

That is the place well described in a lot of legendary stories,

許多傳奇故事都對這座山 做了很好的描述，

like the "Crouching Tiger, Hidden Dragon."

比如《臥虎藏龍》。

That is the place I call home.

那是我稱為家的地方。

Growing up in the mountain,

我在山中長大，

I started to have a strong connection with nature.

我開始和大自然有強烈的連結。

This is me when I was seven years old

這是我七歲的時候，

standing in front of an ancient Buddhist temple

站在一座古老的佛教寺廟前，

with a monkey on my shoulder.

肩上有一隻猴子。

I still vividly remember how my friends and I

我仍然能很鮮明地記得 我和我的朋友

would toss peanuts around to distract the monkeys

如何向周圍丟花生， 來引開猴子的注意力，

so that we could cross to hike through the valley.

這樣我們才能通過，去山谷中健行。

I love nature.

我愛大自然。

When it was time to choose a field of study,

在要選擇研讀領域的時候，

I chose to study biology at Peking University in Beijing.

我選擇在北京大學研讀生物。

However, the more I learned,

然而我學得越多，就有越多的問題。

the more questions I had.

How could our genetic makeup be so similar to animals

怎麼可能我們的基因構造 和動物如此相似，

and yet we look so different?

外表上卻差這麼多？

How is our immune system capable of fighting off so many pathogens

為什麼我們的免疫系統 能夠抵抗這麼多病原體，

but smart enough not to attack ourselves.

卻聰明到不會攻擊我們自身？

Questions like this tormented me.

像這樣的問題讓我很煩擾。

I know it sounds nerdy, but you know I'm a scientist.

我知道這樣聽起來很宅， 但你們知道我是個科學家。

After college, I decided I didn't want to just ask the questions,

大學之後，我決定 我不想要只是問問題，

I wanted to answer them, so I did.

我想要回答問題， 我也的確就這麼做了。

In 2008, I was lucky enough to be accepted

2008 年，我很幸運，

被哈佛大學的博士班接受，

into the PhD program at Harvard University

and worked with Dr. George Church.

跟著喬治丘奇博士研究。

While working in Church's lab,

在丘奇的實驗室中工作時，

I started to learn and experiment with the genetic makeup of mammals.

我開始學習和實驗 哺乳動物的基因構造。

Among all the experiments,

在所有的實驗中，

one particular one took me closer to Laika.

有一項實驗特別讓我更靠近萊卡。

In 2013, my colleagues and I made changes in a human cell

2013 年，我和同事 改造了人類的細胞，

using a tool you may have heard about

我們用的工具各位可能有聽過，

called CRISPR.

叫 CRISPR。

We were one of the first two groups

最早提出成功使用這種工具

to report the successful use of such a tool in changing our DNA.

改變人類 DNA 的兩個團隊， 其中一個就是我們。

It was an exciting moment in scientific discovery.

那是科學發現的一個興奮時刻。

The gene-editing tool CRISPR has two components.

CRISPR 是種基因編輯工具， 它有兩個元件。

It has a scissor called the enzyme CRISPR

它有一把剪刀， 叫做酵素 CRISPR，

and what is called a guide RNA.

還有所謂的嚮導 RNA。

Think about it as genetic scissors with a microscope.

把它想成是有顯微鏡的基因剪刀。

The microscope is a guide RNA,

顯微鏡是一個嚮導 RNA，

which brings the scissors to the place we want to cut

能把剪刀帶到我們想要剪的地方，

and says, "Here it is,"

然後說「就是這裡」，

and the enzyme CRISPR just cuts and repairs the DNA in the way we want.

接著酵素 CRISPR 就會剪下去，

並以我們希望的方式 來修復該 DNA。

Shortly after we reported our study,

在我們提出了我們的 研究之後沒多久，

physicians at Mass General Hospital were intrigued by the medical applications

麻省總醫院的醫師對於我們的研究

在醫療上的應用很感興趣。

of our research.

They reached out to us,

他們跟我們聯絡，

and together, we began to see the potential to use CRISPR

我們合作之後，開始發現 是有可能使用 CRISPR

to solve the organ shortage crisis.

來解決器官短缺的危機。

How do we do it?

我們要如何做到？

It is simple, yet very complex.

很簡單，卻也很複雜。

We started by making changes in a pig's cell to make it virus-free

我們開始改變豬的細胞，

讓它變成沒有病毒， 且和人類免疫系統能夠相容。

and human-immune-compatible.

The nucleus of that cell is then implanted into a pig egg

接著，把那細胞核 植入豬的卵細胞中，

and allowed to divide into an embryo.

讓它分裂成胚胎。

The resulting embryo is then placed into the uterus of a surrogate mother

接著把產生出的胚胎 放到代理孕母的子宮中，

and allowed to divide into a pig.

讓它分裂成一隻豬。

Basically, it's a process of cloning.

基本上，它是一個複製的過程。

The piglet then carries organs whose genetic makeup

這些器官接著就會生長在小豬身上，

hopefully wouldn't be rejected by the human immune system.

希望它們的基因構造不會 被人類免疫系統給排斥。

In 2015, our team decided to tackle the viral transmission problem first.

2015 年，我們的團隊決定

先處理病毒傳播的問題。

We wanted to take out all 62 copies of the PERV virus

我們想要從豬的基因組當中取出

所有 62 個 PERV 病毒的複製品，

from the pig genome,

but at the time, it was nearly mission impossible.

但在當時，那幾乎是不可能的任務。

Even with CRISPR,

即使有 CRISPR，

we could only do one or two modifications within a cell.

我們也只能在一個細胞中 做一或兩種修改。

The record for number of modifications we can do in a particular cell was five.

在一個細胞中，我們所能達到的

最高修改數量記錄是五。

We had to increase the throughput by more than tenfold to achieve that.

我們得要將總處理能力 增加十倍以上才能達成目標。

With very careful design and hundreds of trials,

經過非常小心的設計 和數百次的試驗，

we successfully took out all the virus,

我們成功取出了全部病毒，

broke the record.

打破了記錄。

More importantly, our studies showed

更重要的是，我們的研究顯示，

that we could eliminate the possibility of this dangerous virus

我們可以消除這種危險病毒

傳給人類的可能性。

being transmitted into humans.

Last year, with a modified cell and cloning technology,

去年，用修改過的細胞 以及複製技術，

our startup, eGenesis, produced Laika,

我們的新創公司 eGenesis 產出了萊卡，

the first pig of its kind born without PERV.

牠是第一隻生出來 就沒有 PERV 的豬。

(Applause)

（掌聲）

Laika represents the first critical step

萊卡代表的是關鍵的第一步，

in establishing safe xenotransplantation.

朝向建立安全異種器官移植邁進。

It is also a platform

牠也是個平台，

that we can do further genetic modification on

我們可以在上面 做進一步的基因修改，

to solve the immunology problem.

來解決免疫學問題。

Since then, we have created more than 30 pigs without PERV,

從那之後，我們已經創造出了 超過 30 隻沒有 PERV 的豬，

and they may be the most advanced geno-modified animal living on earth.

牠們可能是地球上 最先進的基因改造動物。

We named Laika after the Soviet dog

萊卡這個名字是取自第一隻

who was the first animal to orbit the earth.

進入環繞地球軌道的蘇聯太空犬。

We hope Laika and her siblings

我們希望萊卡和牠的手足們

can lead us into a new frontier of science and medicine.

能領導我們進入 科學和醫學的新領域。

Imagine a world where patients who suffer from liver failure

想像一個世界， 在那裡，肝衰竭的病人

can be saved with a new liver

可以得到新的肝，因而得救，

without having to wait for a donation

不需要等待捐贈， 也不用等待另一個人死亡。

or another human to die.

Imagine a world where people with diabetes

想像一個世界， 在那裡，有糖尿病的人

do not have to rely on insulin after every meal

不需要仰賴每餐後的胰島素，

because we can provide them with good pancreatic cells

因為我們能夠提供他們 好的胰臟細胞，

that can produce insulin on their own.

那些細胞自己就可以產生胰島素。

And imagine a world where patients with kidney failure

想像一個世界， 在那裡，腎臟衰竭的病人，

do not have to face the burden of dialysis.

不需要面臨洗腎的沉重負擔。

We are striving to create that world,

我們在努力創造那樣的世界，

a world without organ shortage.

沒有器官短缺的世界。

We finally have the tool to tackle the problem

我們終於有了一項工具 可以處理這個問題，

we could never tackle before,

這是以前完全辦不到的，

and Laika is just the beginning of our journey.

萊卡只是我們旅程的開端。

We have to be very humble in front of nature,

在大自然面前，我們得要非常謙虛，

because there are more issues to be addressed,

因為還有更多議題 需要處理，包括免疫學，

including immunology

and things we couldn't even anticipate at this point.

以及我們在這個時點， 我們甚至還無法預期的議題。

However, it is our responsibility to translate the cutting-edge science

然而，我們有責任

要將這尖端科學轉變為醫學，

into medicine to save the lives of all the patients who are waiting.

來拯救所有在等待的病人的性命。

Thank you very much.

非常謝謝。

(Applause)

（掌聲）

Chris Anderson: I mean, Luhan, this is extraordinary work here.

克里斯安德森：璐菡， 這是非常了不起的研究。

Come forward.

請上前來。

So what's the next steps here? You've got rid of the virus.

接下來要做的是什麼？ 你已經解決了病毒問題。

The next steps involve trying to get to the point

接下來要做的是

要試著讓人體不排斥移植。

where a human body won't reject a transplant.

What's involved in solving that?

要解決這問題，會牽涉到什麼？

Luhan Yang: It's a very complicated process.

楊：這是個非常複雜的過程。

So we need to take out the antigen of the pigs.

所以我們得要從豬身上取出抗原。

In addition, we can learn a lot from cancer.

此外，我們也從癌症學到很多。

How can cancer invade or circumvent our immune system

癌症如何能侵入或規避 我們的免疫系統？

so that we can utilize the trick of cancer

我們可能學癌症的技巧，

and implement that on the pig organ

把它用在豬的器官上，

to fool our immune system to not attack the organ.

來愚弄我們的免疫系統， 讓它不去攻擊移植的器官。

CA: When would you estimate, when do you hope

克：依你估計，你希望

that the first successful transplant would happen?

第一次成功移值會在何時發生？

LY: It would be irresponsible for me to give you any number.

楊：我無法給你任何數字， 那是不負責任的行為。

CA: We're at TED. We're always irresponsible.

克：我們在 TED。 我們總是不負責任。

LY: But we are working day and night

楊：但我們日以繼夜地在努力， 試著為病人實現這個夢。

trying to make this happen for the patients.

CA: So not even, you won't say that you think it could happen

克：所以，你甚至 不能說你認為可能會在

within a decade or within five years or something?

十年或是五年之類的期間發生嗎？

LY: For sure we hope it happens within one decade.

楊：當然我們會希望 能在十年內實現。

(Laughter)

（笑聲）

CA: So there's a lot of people here who would be very, very excited at that,

克：這裡有很多人 對此會感到非常興奮，

the potential is extraordinary.

這潛力是非常不凡的。

There will be some other people here who are going,

這裡也會有一些其他的人說： 「那隻豬太可愛了。

"That pig is too cute.

Humans shouldn't be exploiting something so cute for our benefit."

人類不應該利用那麼可愛的生物 來謀求自己的利益。」

Do you have any response to that?

你對這個問題有什麼要回應的嗎？

LY: Yeah, sure.

楊：有，當然。

So imagine one pig can save eight people's lives.

想像一下，一隻豬能夠 拯救八個人的性命。

In addition, similar to human donation,

此外，和人類捐贈很類似，

if we only harvest one kidney from the pig,

如果我們只從豬身上 取得一個腎臟，

the pig can still be alive,

牠仍然能存活，

so we are very mindful about the issues,

我們對於這些議題非常小心謹慎，

but I think our goal is just to address the unmet medical need

但我認為我們的目標只是 要處理尚未滿足的醫療需求，

for those patients and their families.

為了那些病人和他們的家人。

CA: Plus, no one can say that to you if they eat bacon, right?

克：此外，吃培根的人 也不能對你說那種話，對吧？

LY: That's a good point.

楊：說得有理。

(Laughter)

（笑聲）

CA: Luhan, thank you so much. LY: Thank you so much.

克：璐菡，非常感謝。 楊：非常感謝。

(Applause)

（掌聲）