Joshua Chu-Tan: The science of preserving sight | TED

Transcriber:

翻译人员: psjmz mz 校对人员: Thomas Tam

Now to start off today, I want everyone in here to close their eyes

首先，我希望在座各位闭上眼睛

and think about the first thing you saw this morning when you opened your eyes.

回忆一下早上睁开眼睛 第一眼看到的景象。

You know, was it that stain on your ceiling

是一直没清理的天花板上的污渍？

that you keep putting off cleaning?

Was it your partner’s face or your child jumping on top of you?

还是伴侣的脸或是跳到面前的孩子？

Or was it the morning rays of the sun just creeping in through the blinds,

或者是清晨从百叶窗透过来的光线，

that mixture of pink, orange and yellow that signifies the start of a new day.

那粉色、橙色和黄色的混合物 象征着新的一天的开始。

Keep your eyes shut just for a moment longer.

闭上眼睛多一会儿。

And imagine waking up now, but instead of those beautiful images,

想象一下现在醒来， 但没有这些美丽的画面，

all you could see is what you're seeing right now.

你能看到的一切就是现在所看到的。

Darkness.

黑暗。

Those thoughts, those images of the first thing you saw this morning

那些想法， 你早晨看到首个画面

being exactly what it is now,

变成了现在这个样子，

just a memory,

只是个记忆，

an image conjured by your brain from your past.

你的大脑从过去想象出的那张图片。

Now open your eyes.

现在睁开你的眼睛。

When I asked people what the one sense that they couldn't live without is

当我问人们没有哪个感官就没法活时，

most people immediately say, their sight.

绝大多数人马上会说，他们的眼睛。

And you can understand why that is.

你能理解为什么。

I mean, our vision and what we see

我们的视力及看到的东西

play such an integral role in how we perceive the world around us.

在我们感知周遭世界上 扮演着如此必需的角色。

Just look at how much we spend on buildings,

只需要看看我们花了多少时间

on parks, on architecture, on things just to please our visual sense.

在大楼、公园、建筑， 在取悦我们视觉感官的事物上。

But what if we can't see?

但如果我们不能看见呢？

What if we lose this gift?

如果我们失去了这个天赋呢？

What if slowly but surely,

如果慢慢但避免不了，

your visual field looks something like this?

你的视觉区看东西像这个样子呢？

Well, this is exactly what happens

这的确是出现在

in age-related macular degeneration, or AMD.

老年性黄斑变性，或AMD上的事情。

This disease is the leading cause of blindness in the developed world.

这个疾病是发达国家中 引发失明的首要致因。

This disease affects one in seven New Zealanders over the age of 50,

这个疾病影响了50岁以上 新西兰人7个里面的1个。

and yet the most common form of this disease has no cure.

然而这种疾病最常见病状 却没有治愈方法。

AMD is a serious problem.

AMD是个严重的问题。

But we think we have something that may just be the solution

但我们认为我们可能有了解决方案，

because of tiny molecules called microRNA

因为一种叫做MicroRNA的小分子，

that are incredibly powerful gene regulators.

它们是非常强大的基因调节器。

But first, let's talk a little bit about how we actually see.

但首先，让我们聊一点 我们是如何看见的。

Now that is just a stunning structure, isn't it?

那真是一座让人惊叹的结构，不是吗？

I could stare at it forever,

我可以永远盯着它，

which is ironic because that's what allows me to do so.

有点讽刺的正是 因为这些让我可以这样做。

This is a retina.

这是一个视网膜。

This is the thing that allows us to absorb light bouncing off of objects.

这个东西让我们能够 吸收物体上反射的光。

This is the thing that allows us to define shapes, define edges.

这个东西让我们 能够界定形状、界定边缘。

This is what allows us to see.

这就是让我们看见的东西。

It lines the back of the eye and is multilayered,

它排在眼睛的后面，是多层的，

with each layer containing cells with its own respective role.

每一层含有相应角色的细胞。

Now the cell type I want you to know about today are photoreceptors.

现在這種细胞类型是感光细胞。

And if you break down the word and figure out what they mean,

如果你拆开这个词去理解它们的意思，

photo, meaning light, and receptors, or something that receives.

照片，意味着光，而接收器， 是某种能够接受的东西。

So they receive the light.

所以它们接受光线。

So when the light comes into our eye,

所以当光线进入我们的眼睛时，

it's received by these cells

它们被这些细胞接收

and through a series of processes

并经过一系列的处理

begins to convert it into an electrical signal

开始转换成发送到大脑

that has been sent to the brain.

的电信号。

Eventually, this will form an image.

最终，这会形成一个图像。

This is the first step to our vision,

这是我们视觉的第一步，

to everything we see, to you looking at me right now.

我们看到的所有东西， 就像你们现在所看到了的我。

Now there's a specialized region within the retina known as the macula.

在视网膜里有一个特殊的区域叫做黄斑。

It's approximately 5 millimeters in diameter

它的直径大约5毫米

and houses another even more specialized region known as the fovea.

里面还有一个更特殊的区域， 叫做中央凹。

Now when the light comes into our eye,

当光线进入我们的眼睛时，

it's concentrated to focus on this region of the retina.

它会聚焦到视网膜这个区域。

It's responsible for pretty much all of our useful day to day vision,

它负责我们所有日常的视觉，

from our color perception

从我们的颜色感知

to our high visual detail, to our central vision.

到高视力细节， 及中心视野。

All of this mediated by this tiny region.

所有的这一切都是由 这个小区域介导的。

This is also the region where your photoreceptors begin to die

如果你患有AMD病，也是在这个区域

if you have AMD.

你的光感受器开始丧失。

In fact, a 1.5-millimeter lesion in this area,

实际上，在这个区域1.5毫米的病变，

which is approximately the thickness of a credit card,

相当于一张信用卡的厚度，

will render you legally blind.

会让你法定失明。

Unfortunately, AMD is an incredibly complex disease,

不幸的是，AMD是一种 非常复杂的疾病，

and what this means is if you try and block a single thing

意思是如果你尝试阻挡单个

leading to the disease,

引发疾病的东西，

it's very likely that something else would just come and take its place.

很可能就会有其他东西出来替代它。

Whether that be well establish causes, such as inflammation or oxidative stress,

不管是由于确定的炎症 还是氧化应激，

or things we just don't even know about yet.

或是我们尚未知道的原因。

It's the same issue that faces researchers looking into treatments

这和研究者寻求治疗 各种神经退化性疾病，

for all kinds of neurodegenerative diseases,

如阿尔茨海默氏症或帕金森症，

such as Alzheimer's or Parkinson's.

所面临的是同样的问题。

But what if we could find one therapy that could treat multiple causes?

但如果我们能找到一种 能够应对多种病因的疗法呢？

You know, what if we could get to the root of the disease?

如果我们可以直达疾病的根源呢？

Well, maybe we can, but to get there,

也许我们可以，但要到达那里，

we need to understand just a little bit about genetics.

我们需要了解一点点遗传学的知识。

Now some of you may be familiar with the famous Watson, Crick and Wilkins,

你们有些人可能对著名的华生， 克里克和威尔金斯很熟悉，

who in many ways were the pioneers of DNA as we know it.

他们因在很多方面是DNA的先驱， 而为我们所知。

I'm sure a lot of you will also be familiar

我确定你们很多人也熟悉

with Steven Spielberg's epic movie "Jurassic Park."

史蒂文·斯皮尔伯格的 史诗电影《侏罗纪公园》。

Remember that scene

回忆那个

where they have a preserved mosquito with dinosaur’s blood in it,

他们有一只带有恐龙血液的 保存完好蚊子的情节，

and they use that to create new dinosaurs

他们使用这来创造新的恐龙，

and probably the coolest yet most dangerous theme park of all time.

以及可能是有史以来最酷 但最为危险的主题公园。

Well, a lot of you probably scoffed at that idea,

你们很多人可能会嘲笑那个主意，

but in some ways, genetically speaking, it's actually true.

但在某种程度上， 从遗传学的角度来说，这是真的。

As Francis Crick said, DNA makes RNA,

就如弗朗西斯·克里克所说， DNA制造RNA，

RNA makes protein, and protein makes us.

RNA制造蛋白质，蛋白质制造我们。

This is the central dogma of genetics.

这是遗传学的中心法则。

You can think of DNA as the code,

你可以把DNA想象为编码，

coding for just about everything about us,

关于我们人类的一切的编码，

so it makes us human and not a monkey, a rat or a dog.

所以它让我们成为人， 而不是猴子、老鼠或狗。

So it makes us unique individuals.

所以它使我们成为独特的个体。

It's what makes us who we are,

它是创造我们的东西，

but it is just the code.

但它只是编码。

So without the other components of this central dogma,

所以这个中心法则 如果没有其他部件，

it's just going to sit there like a book waiting to be read.

它不过只是一本等待阅读的书本。

Knowledge from this book just waiting to be implemented.

这本书的知识只是等待被应用。

Now your RNA are your messengers responsible for bringing some of that code

现在你的RNA作为信使， 负责携带着部分编码

and telling our cells,

告诉我们的细胞，

OK, this is what needs to be produced right now.

这就是需要马上生产的。

Then the protein that's made is your functional component,

然后生产的蛋白质 就是你的功能成分，

or your workers, if you will.

或者你的工人，如果你喜欢的话。

You can actually think of this central dogma

你其实可以把这个中心法则

as Swedish flatpack furniture giant IKEA.

想象成瑞典平板家具巨头宜家。

Think of the IKEA warehouse as your DNA,

把宜家仓库想象成你的DNA，

containing all of the code,

包含着各种编码，

all the instructions for how these pieces of furniture will be made,

有所有关于这些家具部件 如何组建的指令，

but nothing is actually assembled yet.

但现在仍尚未组装。

You choose what you need and you come out of the warehouse

你选择了你需要的，带着家具

with a set of instructions for your furniture.

的组装指南走出仓库。

The set of instructions is your RNA, copies and copies of these instructions,

这些指南集就是你的RNA， 这些指南的一串串副本，

leaving the warehouse, telling us exactly how we assemble these pieces of furniture.

离开了仓库，告诉我们 如何准确组装这些家具。

Then the fully functional furniture, whether it be your wardrobe or a couch,

然后功能齐全的家具， 无论是你的衣柜还是沙发，

that's your protein, all assembled, ready to do what they need to do.

那就是你的蛋白质，全组装好了， 准备好做它们该做的事情了。

DNA makes RNA, RNA makes protein, and protein makes us.

DNA制造RNA，RNA制造蛋白质， 蛋白质制造我们。

Now when we talk about a standard gene therapy,

现在当我们聊标准的基因疗法时，

you're often looking at a single target.

往往针对单一的目标。

So gene therapies are fantastic

因此基因疗法对于那些

for diseases that can be attributed to a single gene mutation

由单个基因突变或单个根因 引起的疾病来说

or single root cause.

是极好的。

但像AMD这样的疾病，

But for a disease like AMD,

where there's multiple possible causes,

有多种可能的原因，

it's just not as useful at this point in time.

在目前的情况下就没那么有用。

But there's another type of RNA called microRNA.

但有另一种叫microRNA的RNA。

And instead of coding for the creation of protein,

它们不是为蛋白质的生成编码，

these microRNA can actually control which RNA are being read.

这些microRNA其实控制着 哪个RNA被读取。

They are incredibly powerful molecules,

它们是不可思议的强大分子，

with a single microRNA having the ability

一个microRNA，有能力

to control up to 200 different targets

控制多达200个不同的目标，

in what is known as negative regulation.

这就是所谓的负面监管。

这个的意思是当它和一个RNA结合时，

What this means is that when it binds to an RNA,

it stops it from being read and the protein from being produced.

它使RNA停止被读取， 于是蛋白质也就不被制造了。

So let's go back to IKEA.

所以让我们回到宜家。

Imagine microRNA as an officer roaming the car park of IKEA,

把microRNA想象成在宜家停车场 漫游的长官，

checking everything that's coming out of the warehouse

检查离开仓库的每一件东西

for a particular type of furniture.

以搜索特定类型的家具。

Now notice I say type.

注意我说的是类型。

This is what I mean by a pathway.

这就是我说的通路。

So let's say we're suffering from a coffee table epidemic

比如说我们正遭受一场 咖啡桌流行病，

where people are just cluttering their living rooms

人们在客厅中杂乱地

with coffee tables upon coffee tables upon coffee tables for no apparent reason.

没有任何明显原因地 叠着一张又一张的咖啡桌。

Now IKEA will sell hundreds of different kinds of coffee tables,

宜家会卖掉数百张不同类型的咖啡桌，

but they're all still coffee tables serving the same general function.

但它们仍然是咖啡桌 有着同样通用的功能。

A microRNA officer will recognize this

一个microRNA长官将会识别这个，

and specifically get rid of all coffee table instructions.

并特地清掉所有咖啡桌指南。

Doesn't matter the shape, the size or the color.

不管它们的形状、大小或颜色。

If it’s a coffee table, the instructions will no longer be read,

如果是咖啡桌，指南就不能再被读取，

and it will no longer be assembled.

也就永远不能被安装了。

This is how microRNA work.

这就是microRNA的工作。

They can regulate multiple genes from the same pathway,

它们能够从同一个通路监管多个基因，

and this is why they are so powerful

这也是它们如此强大的原因，

because we now have the ability to control an entire pathway

因为我们现在有能力控制整个通路

rather than a single gene on it.

而非上面的单个基因。

MicroRNA have only really been discovered since the turn of the century,

microRNA是本世纪初才被发现的,

and yet there are already multiple microRNA-based therapeutics

但已经有多种针对诸如癌症这类复杂疾病

and clinical trials for complex diseases such as cancer.

的基于microRNA的疗法和临床治疗。

This shows their potential.

这显示了它们的潜力。

This shows their rapidness in going from the lab bench

这显示了它们从实验室工作台

to the clinical bedside.

到临床病床的快速发展。

So let's recap.

让我们回顾一下。

We have an incredibly complex disease known as age-related macular degeneration,

我们有非常复杂的疾病如老年性黄斑变性

or AMD.

或AMD。

A disease that affects the central vision

这种影响中央视觉的疾病

with the most common form having no known cure or treatment.

的最常见形式仍没有治愈或治疗方法。

We have DNA, code that makes us us.

我们有DNA，这种创造我们的编码。

We have RNA messengers for the creation of protein,

我们有RNA信使来制造蛋白质，

and then we have microRNA, controllers of this process.

然后我们有microRNA控制这个过程。

So in order to decide which microRNA might be effective in AMD,

于是为了确定哪个microRNA 可能对AMD有效，

we used a technique that allowed us to figure out

我们使用了一种技术来搞明白

all of the active microRNA in the retina and the targets they're controlling.

所有在视网膜中的活跃microRNA 以及它们所控制的目标。

Using this technique, we found there’s a particular microRNA

使用这种技术，我们发现有一种叫做

known as microRNA-124,

microRNA-124的特别microRNA，

our hero of the story.

故事中的英雄。

124 was far and wide the most abundant and active microRNA

124是我们在视网膜中发现的

that we found in the retina.

最丰富和活跃的microRNA。

It's definitely playing a role.

它确实发挥了作用。

In fact, we found that it's playing an anti-inflammatory role.

实际上，我们发现它扮演着抗炎作用。

This is one of the pathways that it acts on.

这是它作用的一个通路。

So it controls the production of highly inflammatory molecules

所以当视网膜压力过大时，

when the retina gets too stressed.

它控制着高抗炎分子的生产。

124 is strong.

124很强大。

It's a great worker, helps the greater good.

是个强大的工人，有很大的益处。

Exactly like a hero should.

就像英雄那样。

So we looked in the retinas of AMD patients

于是我们望向AMD病人的视网膜，

and what we found was this.

我们发现了这些。

124, stained in red,

染成红色的124，

was completely absent from the central retina of AMD patients

跟健康的人相比， 它们在AMD病人的中央视网膜中

compared to a healthy individual.

完全消失了。

Completely.

完全。

还记得你视网膜中的那部分

Remember the part of your retina

responsible for pretty much all of our useful vision?

几乎负责你全部有效的视觉吗？

Well, 124 is missing there.

124在那里消失了。

And this is what we think is happening.

我们认为发生了这些。

124 is the most active microRNA in the retina,

124是视网膜中最活跃的microRNA，

meaning that it's working a lot even in a disease state,

意味着它在疾病状态也工作繁重，

fighting off danger molecules,

与危险分子，

inflammatory molecules that will cause even more harm.

那些会引发更多伤害的炎性分子作战。

Now the retina recognizes this

视网膜识别出这些分子，

and activates more and more of our 124.

并且激活越来越多的124。

However, the retina eventually gets overwhelmed.

然而，视网膜最终会不堪重负。

Tragically, our heroes can no longer keep fighting

悲剧的是，我们的英雄无法继续战斗

and start dying off

开始死亡

to the point where they are completely absent.

直至完全消失殆尽。

Exactly like we see in those AMD patients.

这正是我们在AMD病人上看到的。

The enemies keep coming.

敌人继续涌来。

124, though, no more, missing in action.

不过，124，不再有，无法行动。

And as a consequence, our retina suffers.

结果，我们的视网膜受罪了。

Our vision suffers.

我们的视力变差了。

So in a study we published last year,

于是在我们去年发表的一个研究中，

we supplemented 124 to animals that have undergone retinal damage.

我们给正遭受视网膜损坏的动物 补充了124.

And through an injection of these molecules into the eye,

通过将这些分子注入眼睛，

what we saw was that animals receiving the treatment

我们看到接受治疗的动物

had better retinal function,

有了更好的视网膜能力，

had less photoreceptor cell death

更少的感光细胞死亡

and had less inflammation.

和更少的炎症。

These are preliminary experiments but a very promising start at that.

这些都是初步实验， 但是一个非常有潜力的起步。

Our next step is to carefully analyze all of the targets

我们的下一步是仔细分析所有这些

that this 124 acts to control.

124控制的目标。

And we're also particularly interested

并且我们也对这些

in how it is that these microRNA travel in the retina

microRNA在视网膜中作为细胞间

as a form of communication between cells.

的一种通信方式如何移动。

Now what do I mean by this?

这是什么意思呢？

Well, we mainly focused on photoreceptors,

我们主要聚焦在光感受器，

but the retina is an interconnected network,

但视网膜是一个相互连接的网络，

with every cell contributing to its overall function.

一个个细胞构成整体的功能。

In this same study,

在这个相同的研究中，

we found that 124 moves from the photoreceptor cells

我们发现124从光感受器细胞

to another cell type,

移动到另一细胞类型，

but only after the retina is damaged.

但只在视网膜损坏后。

Too often we kind of look at what's happening in the cells,

我们常常看着细胞中发生的事情，

completely forgetting there's actually a space in between them.

却往往忘记了它们之间存在空间。

So if we can harness this

所以如果我们能够驾驭

and discover how and why these microRNA move between cells,

和发现microRNA如何 和为什么在细胞间移动，

then we can engineer a deliverable vehicle

那么我们就能够设计出运载工具，

to transport the microRNA that we want exactly where we want it.

传送microRNA到我们想让它去的地方。

Now I want everyone to have a look at this image again.

现在我想让大家再看看这些图片。

And imagine living the rest of your life with vision like this.

想象余生生活在这样的视觉中。

So next time you're with your loved ones,

所以下次你和你爱的人一起时，

study their faces, their every feature.

研究他们的脸蛋，他们的每一个特征。

Next time you wake up in the morning,

下次你早晨起来，

pay attention to every single detail of what you're seeing.

注意你看到的每一个细节。

Use that gift of sight

使用天赋的视觉

and cherish these memories.

并珍惜这些回忆。

Because as I said,

因为像我说的，

one in seven of you will lose this ability if nothing is done about this disease.

七分之一的人将会失去这个能力， 如果对这个疾病无计可施。

With an aging demographic in current times,

随着时下的老龄化，

our society seems to be very concerned about living longer

我们的社会似乎非常关心活得更久

and extending our lifespan.

延长我们的寿命。

But this is so wrong.

但这全然错了。

Trust me when I say this.

相信我说的。

Longevity is not the answer.

长寿不是答案。

Quality is the answer.

质量才是答案。

It's not about --

这无关——

(Applause)

（鼓掌）

It's not about how long we can live, no.

这无关我们能活多久，不是的，

It's about how long we can live well.

这关于如何活着更长更好。

And with the use of microRNA

通过对microRNA的使用，

our hope and our goal is that for millions of people,

我们的希望和目标是让数百万的人，

this image can become clearer

让这张图片能够变得更清晰

for longer.

更长久。

Thank you.

谢谢。

(Applause)

（鼓掌）