My Quest to Cure Prion Disease — Before It’s Too Late | Sonia Vallabh | TED

翻译人员: Fanglin ren 校对人员: Bruce Wang

I'm here because of a letter I got 13 years ago.

我来这里是因为 13 年前 我收到的一封信。

A letter from the future.

一封来自未来的信。

This is it.

就是这样。

It's a predictive genetic test report.

这是一份预测性基因测试报告。

And it's at the heart of this sort of red pill-blue pill moment

这正是这种红色药丸蓝色药丸

when my life forked in two.

时刻的核心，当时我的生命一分为二。

Before I tell you about that,

在我告诉你这件事之前，

I want to show you two moments from my life back then.

我想向你展示我当时生活中的两个时刻。

This is moment number one. It's August 2009.

这是第一时刻。 现在是 2009年 8 月。

I’m marrying this guy, Eric, love of my life.

我要嫁给这个人，埃里克，我一生的 挚爱。

And he gets up there to give his speech

然后他到那里发表演讲

and he's holding my diary from when I was 13.

他手里拿着我 13 岁时的 日记。

And he starts reading from it, and the guests are looking at me like,

然后他开始读书， 房客们看着我，

"Did she know he was going to do this?"

“她知道他会这样做吗？”

Guys, if you're watching, I knew.

伙计们，如果你们在看，我就知道了。

OK, this is me and my mom.

好吧，这是我和我妈妈。

You can see how she’s laughing but she’s kind of scandalized.

你可以看到她笑的样子， 但她有点愤怒。

(Laughter)

（笑声）

She’s 51 years old and on this day, she is glowing.

她已经 51岁了 ， 在这一天，她正在发光。

I wish I could stay here with you.

我希望我能待在你身边。

But now I have to take you to moment number two.

但是现在我必须带你 进入第二刻。

It's only six months later,

仅仅六个月后，

and suddenly there's this tear in the universe,

宇宙中突然出现了这滴眼泪，

and my mom is being sucked through it.

我妈妈被吸走了。

No one can tell us what's wrong, but something is really, really wrong.

没有人能告诉我们出了什么问题， 但是确实有些不对劲。

And it is snowballing. And it is everything.

而且它正在滚雪球。 而这就是一切。

She's confused about who she is,

她对自己是谁、

where she is.

在哪里感到困惑。

She's scared. She's hallucinating.

她很害怕。她在幻觉。

She is too weak to walk.

她太虚弱了，没法走路。

This is happening on a timescale of weeks.

这是在几周的时间范围内发生的。

I’m looking into her eyes, and they are these black holes,

我正在注视她的眼睛， 它们是这些黑洞，

and I am begging her to come back, but it's like I'm shouting into the void.

我求她回来， 但这就像我在虚空中大喊大叫一样。

That summer, she goes into the hospital, and she doesn’t come out.

那年夏天，她进了医院， 却没有出来。

By the time she dies,

当她去世时，

it has been months since she was really there.

她已经有几个月 没有真正存在了。

We don't get a present tense goodbye.

我们不懂现在紧张的再见。

Dementia has robbed us of that.

痴呆症使我们失去了这一点。

And we still have no idea what happened.

而且我们仍然不知道发生了什么。

And then we get the results of my mom's autopsy.

然后我们得到了我妈妈的尸检结果。

And this is where we reach the red pill and the blue pill.

这就是我们得到红色药丸和蓝色药丸的地方。

The report tells us that my mom died of genetic prion disease.

报告告诉我们，我妈妈 死于遗传性朊病毒病。

And that I am at 50-50 risk

而且我遗传了导致它的单字母DNA错字

of having inherited the single-letter DNA typo that caused it.

的风险为50-50。

Prion disease kills about 1 in 6,000 people.

朊病毒病 大约每6,000人中就有1人死亡。

But most cases aren't genetic.

但是大多数病例不是遗传的。

They're random.

它们是随机的。

So it's maybe 1 in 50,000 people

因此，可能每5万人中

that has a high-risk mutation like this one.

就有1人患有 这样的高风险突变。

I stand at this fork in the road with Eric.

我和埃里克一起站在这个岔路口。

And sometimes in life you know yourself.

有时候，在生活中你认识自己。

We realize there is no fork.

我们意识到没有叉子。

We want to know.

我们想知道。

I'm trained as a lawyer. He's trained as a transportation engineer.

我受过律师培训。 他受过运输工程师的培训。

We are not biomedical people,

我们不是生物医学人士，

but we know that for us, this limbo isn't life.

但我们知道对我们来说， 这种困境不是生命。

I can't control what happens next,

我无法控制接下来会发生什么，

but I can control whether something happens next.

但我可以控制接下来 是否会发生什么。

And my choice is yes.

我的选择是肯定的。

So I get tested, and we learn that I have the mutation.

所以我接受了测试，我们得 知我有突变。

(Sighs)

（叹气） 这对我意味着

What does this mean for me? For us?

什么？为了我们？

Genetic prion disease is always fatal.

遗传性朊病毒病总是致命的。

We can't say when it will strike,

我们无法说它何时会发作，

only that it will be some point in adulthood,

只能说它将是成年的 某个时刻，

and once it does, you die in months.

一旦发生，你将在几个月后死亡。

We have just watched it happen.

我们刚刚目睹了它的发生。

There's so much I want to tell you about what happens next,

but the main thing to say

但要说的主要是，

is that it's not like we hatch some master plan

这不像我们在策划一些总体规划

to remake our lives overnight.

来一夜之间重塑我们的生活。

It's not that dramatic.

没那么戏剧化。

It's more plantlike.

它更像植物。

We’re in the dark, and we find ourselves growing towards the light.

我们在黑暗中，我们发现自己正朝着光明的方向成长。

And unexpectedly the light is coming

出乎意料的是，

from the science of prion disease.

光线来自朊病毒病的科学。

Understanding what is known, that anything is known --

了解什么是已知的， 任何事物都是已知的——

we are drawn to it.

我们被它吸引。

And this is really humble at first,

起初这真的很谦虚，

like we're reading Wikipedia pages and we're doing Google searches,

就像我们在阅读维基百科页面， 我们在做谷歌搜索一样，

and the momentum is powerful and strange.

而且势头强大而奇怪。

We invite scientist friends over to teach us stuff,

我们邀请科学家朋友来教我们一些东西，

and we sign up for night classes,

然后我们报名参加夜间课程，

and we leave our careers for entry level lab jobs.

然后我们离开自己的职业生涯，转 而从事入门级实验室工作。

And we go back to school to get our PhDs in biological and biomedical sciences.

然后我们回到学校攻读生物和生物医学博士学位。

And today, we're leading this lab of twelve people

今天，我们在马萨诸塞州剑桥 的布罗德研究所领导

at the Broad Institute in Cambridge, Massachusetts,

着这个由十二人组成的实验室，

devoted to developing a therapy for prion disease in our lifetimes.

致力于开发我们一生中朊病毒病的疗法。

(Applause)

（掌声）

Thank you.

谢谢。

That's our life.

这就是我们的生活。

And --

而且 ——

Leading this life has certain liabilities.

过上这种生活有一定的责任。

Like ...

就像...

things can get macabre if you Google search my name.

And if you click on "obituary," dang.

如果你点击 “讣告”，该死。

Bottom line, rumors of my death have been greatly exaggerated.

最重要的是，关于我死亡的传闻被大大夸大了。

(Laughter)

（笑声）

OK, but let's talk about how prion disease works

好的，但让我们来谈 谈朊病毒病是如何运作的，

and what we need to do about it.

以及我们需要做些什么。

Prion disease is unique in all of biology.

朊病毒病在所有生物学中都是独一无二的。

The causal pathogen isn’t a virus, and it’s not a bacterium.

因果病原体不是病毒，也不是细菌。

It's this one normal protein called PrP that you normally have in your body.

这是你体内通常含有的一种叫做PrP 的普通蛋白质。

And it's normally not a problem, but it is capable of going rogue.

这通常不是问题， 但它能够成为盗贼。

And when it does, it changes shape.

当它发生时，它会改变形状。

And then it goes around grabbing other copies of PrP,

然后它开始 抓取 PrP 的其他副本，

and it corrupts those.

它会腐蚀他们。

And this spreads through your brain and kills your neurons.

这会传播到你的大脑中 并杀死你的神经元。

Until recently, this was a process we could only infer.

直到最近，这个过程 我们只能推断。

But now, thanks to state-of-the-art single-molecule imaging,

但是现在，得益于最先进的 单分子成像，

we can observe it directly.

我们可以直接对其进行观察。

Shown here at TED for the first time,

这是我第一次在TED上映，

I am so pleased to present to you the prion misfolding cascade in action.

我很高兴向大家介绍一下正在运行 的朊病毒错误折叠的瀑布。

(Laughter)

（笑声）

They like the joke. OK. I knew we were going to get along. OK.

他们喜欢这个笑话。好吧。 我知道我们会相处的。好吧。

I swear I have a point, though.

但我发誓我有道理。

When you look at the biology of this disease, any disease,

当你观察这种疾病 的生物学时，任何疾病，你的眼睛会去

where do your eyes go?

哪里？

They go to the train wreck. Right?

他们去火车失事处。对吧？

Look at those scary rogue proteins.

看看那些可怕的盗贼蛋白。

And if we think about how to treat this disease,

如果我们考虑 如何治疗这种疾病，

we might think, go get those bad guys.

我们可能会想，去找那些坏人。

Pew, pew! Yeah. Like that.

Pew，pew！是啊。像这样。

But Eric and I have come to see our mission differently.

但是埃里克和我对 我们的使命有了不同的看法。

What if we can do the most good

如果我们能做到最大的好处，

not by going after

不是通过追

the big scary pathogens

捕可怕的大病原体

and lobbing fireballs at them,

并向它们投掷火球，

but instead by doing something much more understated and subtle,

而是做一些更低调、 更微妙、不那么性感、

and less sexy and less conventional.

不那么传统的事情。

What if what we really need to do is this?

如果我们真正需要做的是这样呢？

Long before disease begins,

早在疾病开始之前，

we use a drug to ask this not-yet-pathogenic protein

我们就使用一种药物来要求

to please go away.

这种尚未致病的蛋白质消失。

We're lucky to have the series of clues from nature

我们很幸运能从大自然中获得 一系列线索，这些线索

that indicate you can live a healthy life without PrP.

表明没有PrP你就能过上健康的生活。

So we’re scouring the globe for tools to dial it down.

因此，我们正在全球范围内 搜寻可以降低频率的工具。

And brilliant ideas are an awesome start,

绝妙的想法是一个不错的开端，

but they also have to be wrangleable into actual, practical medicines

但它们也必须能够 转化为实际的、实用的药物，

that stay in the body long enough to be useful

这些药物在体内停留足够 长的时间才能有用，

and are safe and manufacturable and -- very tricky for the brain --

并且是安全和可制造的，而且，对大脑来说 非常棘手，

get to the cells we need to reach.

可以找到我们需要触及的细胞。

It's a complicated search.

这是一个复杂的搜索。

But I do just want to assure you,

但我只想向你保证，

because I see you twitching, wanting to ask me,

因为我看见你在抽搐， 想问我，

I promise we most definitely have heard of CRISPR.

我保证我们肯定听说 过CRISPR。

OK.

好吧。

(Laughter)

（笑声）

So you take the molecule, right? We find the molecule.

所以你拿这个分子，对吧？ 我们找到分子。

And then we deploy it to deplete the fuel before the fire.

然后我们在火灾发生之前部署它 来消耗燃料。

Why get hung up on timing?

为什么要挂断时机？

Because your brain isn't any other organ.

因为你的大脑不是任何其他器官。

Your brain is what makes you you.

你的大脑造就了你。

Our greatest good isn't a drug that will stabilize me or anyone else

我们最大的好处不是 一种能稳定我或其他任何人一只脚在

mid-train wreck, one foot in the void.

空隙中失事的药物。

Where we have letters from the future to guide us,

当我们有 来自未来的信件来指导我们，

where what's at stake is irreplaceable human brains,

危在旦夕的是不可替代的人脑的地方，

we have to aim higher.

我们必须瞄准更高的目标。

We have to prevent.

我们必须防止。

Come to find out, prevention isn't business as usual.

来了解一下， 预防不是一成不变的。

Clinical trials are basically always done in sick patients post-train wreck.

临床试验基本上都是在列车失事后的病人身上进行 的。

This is what's comfortable.

这才是最舒服的。

But we all know if you're having a heart attack

但是我们都知道， 如果你心脏病发作

and you walk into the ER at that moment

然后那一刻你走进急诊室

and they give you a statin, it won't help.

然后他们给你服用他汀类药物，那也无济于事。

Prevention and treatment are different goals.

预防和治疗 是不同的目标。

And some of us don't have the luxury of doing only what's comfortable.

而且我们当中有些人无法奢侈 地只做舒适的事情。

I see this paradox at the heart of our mission.

我认为这个悖论 是我们使命的核心。

For sure, we are being summoned to be audacious.

当然，我们被要求大胆行事。

We know so much more about the brain and how to get drugs there

与几年前相比，我们对大脑 以及如何从那里获取药物的了解

than we did even a few years ago.

要多得多。

We know so much about prion disease.

我们对朊病毒病了解很多。

Not everything, but we have enough bricks in the wall

不是所有东西，但是我们的墙

that we can stand on them and reach for a rational therapy.

上有 足够的砖头可以站在上面， 寻求合理的疗法。

We have to be the people to say the biotechnological moment is ripe.

我们必须是人民才能说 生物技术的时机已经成熟。

It's time to dare greatly.

现在是大胆尝试的时候了。

And ...

和...

equally ...

同样...

we have to respect the vastly larger universe

我们必须尊重 这个大得多的宇宙，里面有我们

of everything we don't know about the brain.

对大脑一无所知的一切。

We have to heed the call to protect what we can't rebuild.

我们必须听从呼吁， 保护我们无法重建的东西。

The hutzpah and the humility.

胡兹帕和谦卑。

Our quest requires this kind of extreme form of both.

我们的追求需要 这种极端的两者兼而有之。

So what is daily life like in the trenches?

那么战沟里的日常生活是什么样子呢？

A decade ago, if you had asked me,

十年前，如果你问我：

"Sonia, what's the holy grail of your quest?"

“索尼娅，你追求的圣杯是什么？”

I would have said it's that molecule I told you about.

我本来可以说是我跟你说的那个分子。

We need the structure of the molecule.

我们需要分子的结构。

But what if finding the molecule isn't enough?

但是，如果找到分子还不够呢？

It turns out to meaningfully test a new medicine in humans,

事实证明，在人体内测试 一种新药是有意义的，

especially for rare disease and especially for prevention,

尤其是针对罕见疾病 的药物，尤其是预防药物，

you need more, you need a lot more.

你需要更多，需要更多。

And if you're us, you need to be building it all in parallel

而且，如果你是我们，你需要把它全部并行构建，

because you are racing against the clock you can't see.

因为你在与时间赛 跑，你看不见。

So before our eyes, our scope has expanded from this ...

因此，在我们眼前， 我们的范围已经扩大了...

to this.

对此。

It's a lot.

很多。

(Laughs)

（笑声）

And maybe you're wondering how it's all going.

也许你想知道一切进展 如何。

Here's what I can say.

以下是我能说的。

There will be the race to the first drug and the race to the best drug.

将有争夺第一种药物 和争夺最佳药物的竞赛。

We’re far from the end of this quest, but we’re far from the beginning.

我们离这个任务还很远， 但我们离起点还很远。

We don't have any guarantees.

我们没有任何保证。

Darn.

该死。

But what we do have,

但是我们所拥有的，

and gosh, are we lucky to have it,

天哪，我们有幸拥有它吗，

is jeopardy!

是危险的！

There's more to say

关于生活在危险之中的感觉，

about what it's like to live with jeopardy,

还有更多话要说，

but as far as I can tell, at least, you all are human,

但据我所知，至少， 你们都是人类，

and so I think on some level, you know.

所以我想在某种程度上，你知道的。

Recently, I told a friend that I consider myself lucky,

最近，我告诉一位朋友， 我认为自己很幸运，

and he gets all surprised.

他全都感到惊讶。

He's like, "Even with the mutation?"

他说：“即使有突变吗？”

And my mind was kind of blown because this is me.

而且我有点震惊，因为这是我。

There's no version of my life where you subtract the mutation

在我的生活中， 没有任何版本可以减去突变

and hold the rest constant.

并保持其余变量不变。

On the one hand, I got dealt a bad card.

一方面，我得到了一张坏牌。

And don't get me wrong, I really don't want to die young.

别误会我的意思， 我真的不想早死。

At the same time,

同时，

this bad card has launched me on a quest with a team.

这张坏牌让我开始与 一支队伍一起任务。

And the wonder of this exact life

而这种生活的奇妙之处在于，

is that I am constantly getting to meet people's best selves,

我能不断地遇见人们最好的自我，

including versions of Eric and me,

包括我和埃里克的版本，

that I wouldn't have encountered any other way.

这是我其他任何方式都不会遇到的。

(Sighs)

（叹气）

Does everything happen for a reason?

一切都是有原因的吗？

I don't know, guys. Probably not.

我不知道，伙计们。可能不是。

And yet here we all are making our own grace

然而，在这里，

out of the darndest raw materials.

我们都在用最糟糕的原材料制造自己的优雅。

It is not such a bad thing to be called to notice.

引起注意并不是一件坏事。

Speaking of grace,

说到恩典，

I want you to meet these guys.

我想让你见见这些人。

These are our kids.

这些是我们的孩子。

Daruka is the big one, Kavari is the also big one.

达鲁卡是大佬， 卡瓦里也是大佬。

We had them through IVF with preimplantation genetic testing

我们让他们接受了试管婴儿 和植入前基因检测，

to avoid passing on my mutation.

以避免我的突变遗传。

The slogan says it all.

口号说明了一切。

(Laughter)

（笑声）

My mom never got to meet these kids,

我妈妈从来没见过这些孩子，

and she would have been a luminous grandma.

她本来会是个聪明的奶奶。

But if she had, we wouldn't have known about my risk in time

但是，如果她有，我们就不会及时 知道我的风险

to avoid passing it on.

以免将其转嫁出去。

So somewhere wrapped up in the grief of having lost her so young

因此，另一件事

is this other thing, this transgenerational gift.

是另一回事，这 份跨世代的礼物， 弥漫在她这么年轻的悲痛之中。

I'm walking alongside these kids on their own journeys as best I can.

我会尽我所能和这些孩子一起踏 上自己的旅程。

And you know how it is with kids.

而且你知道孩子们的处境。

Sometimes the shape of the future begs to be assumed.

有时需要假设未来的形状。

X number of years until Y.

距离Y还有X年。

This parade of milestones. This storyboard.

这场里程碑的游行。 这个故事板。

But here again is a luxury not all of us have.

但是，这又是一种 并非所有人都拥有的奢侈品。

And perhaps, in ways large and small,

也许，无论大小，

it's a luxury none of us have.

这都是我们谁都没有的奢侈品。

What would it mean to do all of this less narratively?

减少所有这些叙事性会意味着 什么？

What if our lives, our lives together,

如果我们的生活，我们的共同生活，最好

are best lived not as prose, but as poetry?

不是像散文一样生活， 而是像诗歌一样生活，会怎样？

I'm still living into this question, but I'm glad to have it with me.

我仍在研究这个问题， 但我很高兴能问到这个问题。

Folks, thank you and wish us luck.

各位，谢谢你们，祝我们好运。

We need it.

我们需要它。

(Applause)

（掌声）

Chris Anderson: That’s, um --

克里斯·安德森：那是，嗯——

That's extraordinary. I've got a question.

太不寻常了。我有个问题。

This is a rare disease,

这是一种罕见的疾病，

but it feels as if some of what you're learning

但感觉好像你

is going to end up applicable to other diseases.

正在学习 的一些东西最终会 适用于其他疾病。

Are you already seeing signs of that?

你已经看到这样的迹象了吗？

Sonia Vallabh: I see it in all sorts of ways.

索尼娅·瓦拉布： 我有各种各样的看法。

And this is how it goes with science, right?

科学就是这样，对吧？

And I see it on many levels.

而且我在很多层面上都看到了这一点。

And, you know, the thing that I would highlight is that --

而且，你知道，我要强调 的是——

Here we are with this disease that is in some ways very black and white.

我们现在的疾病 在某些方面是黑白相间的。

You develop symptoms, and then you die three or six months later.

你出现症状，然后在 三六个月后死亡。

And what's happening?

那发生了什么？

Irreplaceable neurons are dying at an unbelievable rate.

不可替代的神经元正在以令人难以置 信的速度死亡。

So I think we have a case, you know,

所以我认为我们有一个案例，你知道，

here is a monogenic disease, one gene, one protein.

这是一种单基因疾病， 一种基因，一种蛋白质。

We know what we have to do.

我们知道我们必须做什么。

I think we have a strong case to go in and say we need to prevent,

我认为我们有充分的理由 说我们需要预防，

and we have the tools to do it.

而且我们有预防的工具。

But this is not the only disease where that is what we need to do.

但是，这不是唯一一种我们需要做的事情的疾病。

I just think we are in a position to lead the charge.

我只是觉得我们有能力领导冲锋。

CA: The idea that there are other proteins in the body

CA：这样的想法是，人体内

that may be subject to a disease,

还有其他蛋白质可能会受到疾病的影响，

and that it may be that the better thing to do is to take them out

而且最好的办法可能是把它们拿出来，

and figure out how to live without them, than to risk --

弄清楚如何在没有这些蛋白质 的情况下生活，而不是冒险，

that that could be applied in other circumstances.

那样可以应用于其他情况。

Absolutely.

绝对可以。

It's an extraordinary idea. You're an extraordinary person, if I may.

这是一个非同寻常的主意。 如果可以的话，你是一个非凡的人。

Thank you so much for coming. Thank you.

非常感谢你的光临。谢谢。

(Applause)

（掌声）