Siddharthan Chandran: Can the damaged brain repair itself?

翻译人员: liu angela 校对人员: Dong Mao

I'm very pleased to be here today

今天很高兴能在此

to talk to you all about how we might repair

与你们探讨我们如何去修复

the damaged brain,

受损的大脑

and I'm particularly excited by this field,

研究这个领域使我倍感激动

because as a neurologist myself,

因为我本身就是一名神经学家

I believe that this offers one of the great ways

我坚信这项研究足以带来最好的治疗

that we might be able to offer hope

使我们可以将希望带给

for patients who today live with devastating

众多病入膏肓且回天乏术

and yet untreatable diseases of the brain.

大脑疾病的患者

So here's the problem.

那么请看我们面临的问题。

You can see here the picture of somebody's brain

你们可以看到这是一张

with Alzheimer's disease

老年痴呆患者的大脑图

next to a healthy brain,

旁边是健康的大脑图

and what's obvious is, in the Alzheimer's brain,

明显可以看到 老年痴呆的患者的大脑

ringed red, there's obvious damage -- atrophy, scarring.

红色圈出来明显受损的区域——萎缩 有疤痕

And I could show you equivalent pictures

我还可以向你们展示类似的

from other disease: multiple sclerosis,

其他疾病的图片：多发性硬化

motor neuron disease, Parkinson's disease,

运动神经元疾病 帕金森症

even Huntington's disease,

甚至是亨廷顿氏舞蹈病

and they would all tell a similar story.

这些图片大同小异

And collectively these brain disorders represent

这些大脑疾病共同显示了

one of the major public health threats of our time.

当今威胁我们公众健康的主要疾病之一

And the numbers here are really rather staggering.

现在患病人数令人乍舌

At any one time, there are 35 million people today

如今 共有三千五百万人

living with one of these brain diseases,

患有某种脑部疾病

and the annual cost globally

并且全球每年用于治疗这些疾病的花费

is 700 billion dollars.

均高达到七千亿美元

I mean, just think about that.

听听 仔细想想吧

That's greater than one percent

这一数字比全球GDP总额的百分之一

of the global GDP.

还要多

And it gets worse,

情况正变得更糟

because all these numbers are rising

因为这一数字不断攀升

because these are by and large

因为这类疾病总体上

age-related diseases, and we're living longer.

与年龄相关 而我们的寿命在延长

So the question we really need to ask ourselves is,

所以我们真正要问自己的问题是

why, given the devastating impact of these diseases

这类疾病会对个人的造成如此毁灭性的影响

to the individual,

这类疾病会对个人的造成如此毁灭性的影响

never mind the scale of the societal problem,

为什么我们还对此社会问题置若罔闻

why are there no effective treatments?

为什么没有有效地治疗？

Now in order to consider this,

为了思考这类问题

I first need to give you a crash course

我现在必须上一堂让你们抓狂的课

in how the brain works.

关于大脑如何运作的

So in other words, I need to tell you

换而言之 我需要告诉你们

everything I learned at medical school.

我在医学院学到的一切知识

(Laughter)

（笑）

But believe me, this isn't going to take very long.

但是相信我 不会花很长时间的

Okay? (Laughter)

行吗？（笑）

So the brain is terribly simple:

其实大脑很简单：

it's made up of four cells,

它由四种细胞组成

and two of them are shown here.

两个已经展示在这儿 了

There's the nerve cell,

这是神经细胞

and then there's the myelinating cell,

而这是髓鞘细胞

or the insulating cell.

或者是绝缘细胞

It's called oligodendrocyte.

这个被称为少突细胞

And when these four cells work together

当这四种细胞健康和谐地

in health and harmony,

共同工作时

they create an extraordinary symphony of electrical activity,

会产生一种特殊的电流活动

and it is this electrical activity

而正是这种电流活动

that underpins our ability to think, to emote,

加强了我们的能力去思考 去表现自己

to remember, to learn, move, feel and so on.

去记忆 学习 行动 感受等等

But equally, each of these individual four cells

但同样的 每一种细胞

alone or together, can go rogue or die,

单独或者一起 都有可能会失常或死亡

and when that happens, you get damage.

如果发生这种情况 大脑便受损

You get damaged wiring.

大脑的线路会损坏

You get disrupted connections.

大脑间的联系会被切断

And that's evident here with the slower conduction.

这里的活动明显减速了

But ultimately, this damage will manifest

但最终 这种损害将恶化为疾病

as disease, clearly.

但最终 这种损害将恶化为疾病

And if the starting dying nerve cell

如果正走向于死亡的神经细胞

is a motor nerve, for example,

是元神经的话

you'll get motor neuron disease.

你就会患神经元疾病

So I'd like to give you a real-life illustration

我想给你们展示一个现实生活中的例子

of what happens with motor neuron disease.

如果患了神经元疾病会怎么样

So this is a patient of mine called John.

这是我的一个病人叫做约翰

John I saw just last week in the clinic.

我上周才在诊所看到约翰

And I've asked John to tell us something about what were his problems

我让约翰告诉我们是什么样的问题

that led to the initial diagnosis

导致了他最初被诊断为

of motor neuron disease.

患有神经元疾病

John: I was diagnosed in October in 2011,

约翰：我在2011年11月确诊

and the main problem was a breathing problem,

关键的问题出在呼吸上

difficulty breathing.

呼吸很困难

Siddharthan Chandran: I don't know if you caught all of that, but what John was telling us

我不知道你们听懂了没 约翰刚说的是

was that difficulty with breathing

他呼吸困难

led eventually to the diagnosis

最终确诊为

of motor neuron disease.

患有神经元疾病

So John's now 18 months further down in that journey,

现在距离约翰患病过去了18个月

and I've now asked him to tell us something about

我让他告诉你们

his current predicament.

他现在的困境

John: What I've got now is the breathing's gotten worse.

约翰：我现在的呼吸更加了困难了

I've got weakness in my hands, my arms and my legs.

我的双手 胳膊和双脚没什么力气

So basically I'm in a wheelchair most of the time.

所以现在基本上我都坐在轮椅上

SC: John's just told us he's in a wheelchair

约翰刚刚告诉我他大部分时间

most of the time.

都坐在轮椅上

So what these two clips show

所以这两个影音片段不仅证明了

is not just the devastating consequence of the disease,

疾病造成的后果是毁灭性的

but they also tell us something about

并且疾病恶化的速度

the shocking pace of the disease,

也是十分惊人的

because in just 18 months,

因为仅仅只过了18个月

a fit adult man has been rendered

一个健康的成年人就必须

wheelchair- and respirator-dependent.

依靠轮椅和呼吸器度日

And let's face it, John could be anybody's father,

让我们正视这个事实吧 约翰可能是一位父亲

brother or friend.

一位兄长或是朋友

So that's what happens when the motor nerve dies.

所当神经元细胞死亡时就会出现这样的情况

But what happens when that myelin cell dies?

那么如果是髓鳞脂细胞死亡 情况又是怎样的呢？

You get multiple sclerosis.

那就会得多发性硬化症

So the scan on your left

左边的这个扫描图

is an illustration of the brain,

显示的是大脑内部

and it's a map of the connections of the brain,

里面的各种连接

and superimposed upon which

而这块叠加的地方

are areas of damage.

这是受损区域

We call them lesions of demyelination.

我们称之为髓鞘脱失

But they're damage, and they're white.

细胞受损后呈现白色

So I know what you're thinking here.

我知道你们在想什么

You're thinking, "My God, this bloke came up

你们在想 “老天爷呀，这哥们儿跳出来

and said he's going to talk about hope,

说是要谈谈希望

and all he's done is give a really rather bleak

结果尽在这儿谈些惨淡压抑的事儿”

and depressing tale."

结果尽在这儿谈些惨淡压抑的事儿”

I've told you these diseases are terrible.

我确实说过这些疾病很可怕

They're devastating, numbers are rising,

又是毁灭性的 患病人数也在上升

the costs are ridiculous, and worst of all,

花费惊人 最糟的是

we have no treatment. Where's the hope?

我们没法儿治愈 希望在哪儿呢？

Well, you know what? I think there is hope.

但是你们知道吗？我认为希望就在这儿

And there's hope in this next section,

在某个多发性硬化症患者脑部的

of this brain section of somebody else with M.S.,

另一个区域出现了希望

because what it illustrates

因为它展示了

is, amazingly, the brain can repair itself.

大脑的惊人自愈能力

It just doesn't do it well enough.

只是这种能力不是特别强而已

And so again, there are two things I want to show you.

所以 我想再一次的向你展示两幅图

First of all is the damage of this patient with M.S.

首先是多发性硬化症的图

And again, it's another one of these white masses.

另外一张是有白色物质的图

But crucially, the area that's ringed red

但重要的是 用红色圈出的区域

highlights an area that is pale blue.

有浅蓝色的物质

But that area that is pale blue was once white.

但是这片蓝色曾经也是白色的

So it was damaged. It's now repaired.

它之前受损 但现在它自己修复了

Just to be clear: It's not because of doctors.

要明白的是：这不是医生的功劳

It's in spite of doctors, not because of doctors.

这与医生无关 并不是因为他们

This is spontaneous repair.

这是一种自发的修复

It's amazing and it's occurred

令人称奇但确实发生了

because there are stem cells in the brain, even,

因为大脑中的干细胞

which can enable new myelin, new insulation,

能够创造新的髓磷脂 新的绝缘细胞

to be laid down over the damaged nerves.

覆盖在受损的神经上

And this observation is important for two reasons.

这一观察十分重要，有两个原因

The first is it challenges one of the orthodoxies

一是它挑战了医学院所教授的

that we learnt at medical school,

正统权威

or at least I did, admittedly last century,

至少是我上世纪念医学院的时候所接受的教育

which is that the brain doesn't repair itself,

医学院的权威认为大脑不能自我修复

unlike, say, the bone or the liver.

不像是骨头或者是肝脏

But actually it does, but it just doesn't do it well enough.

但大脑确实有这能力只是不够强大而已

And the second thing it does,

二是我们知道大脑有这样的再生机制

and it gives us a very clear direction of travel for new therapies --

这为我们提供了新式治疗的明确方向——

I mean, you don't need to be a rocket scientist

我是说 即使不是造火箭的专家

to know what to do here.

也知道该怎么做

You simply need to find ways of promoting

你只需找到方法来推动

the endogenous, spontaneous repair that occurs anyway.

这一自发性治愈的进程

So the question is, why, if we've known that

问题是 假使我们知道这一事实

for some time, as we have,

我们现在就知道了

why do we not have those treatments?

为什么我们还没有治疗方案呢？

And that in part reflects the complexity

这至少从局部反映出

of drug development.

药品研发的复杂性

Now, drug development you might think of

你们可能认为制药虽然昂贵

as a rather expensive but risky bet,

却值得一试

and the odds of this bet are roughly this:

这一尝试的概率大概是这样的：

they're 10,000 to one against,

万分之一的机会

because you need to screen about 10,000 compounds

因为我们需要从一万种化合物中

to find that one potential winner.

找到可能有效的某一种

And then you need to spend 15 years

这可能需要花上15年时间

and spend over a billion dollars,

以及10亿不止

and even then, you may not have a winner.

即使如此 也可能徒劳无功

So the question for us is,

所以现在的问题是

can you change the rules of the game

我们能否改变游戏规则

and can you shorten the odds?

或者我们能否加大胜算？

And in order to do that, you have to think,

为了达到这一目标 就必须思考

where is the bottleneck in this drug discovery?

药品研发的瓶颈在哪儿？

And one of the bottlenecks is early in drug discovery.

瓶颈之一就是在制药发现的早期阶段

All that screening occurs in animal models.

所有的筛选都以动物为研究对象

But we know that the proper study of mankind is man,

但是我们知道研究人类才是合适的

to borrow from Alexander Pope.

这句话出自亚历山大蒲伯之口

So the question is, can we study these diseases

问题是 我们能用人类的材料

using human material?

来研究这些疾病吗？

And of course, absolutely we can.

当然 我们绝对可以

We can use stem cells,

我们可以利用干细胞

and specifically we can use human stem cells.

具体就是说我们可以利用人类干细胞

And human stem cells are these extraordinary

人类干细胞是十分特别

but simple cells that can do two things:

但也很简单的细胞 能做两件事情：

they can self-renew or make more of themselves,

干细胞能自我更新或者自我利用

but they can also become specialized

但是他们能变得更细化

to make bone, liver or, crucially, nerve cells,

分裂出骨骼细胞 肝脏细胞 最重要的是神经细胞

maybe even the motor nerve cell

甚至是神经元细胞

or the myelin cell.

或者是髓磷脂细胞

And the challenge has long been,

长期以来的挑战都是

can we harness the power,

我们能否驾驭这种力量

the undoubted power of these stem cells

驾驭干细胞毋庸置疑的力量

in order to realize their promise

去开发细胞的潜能

for regenerative neurology?

发展再生长神经学？

And I think we can now, and the reason we can

我认为我现在有能力了 原因就在于

is because there have been several major discoveries

在过去的10年20年中有了

in the last 10, 20 years.

些许重大的发现

One of them was here in Edinburgh,

其中一个便是在这儿 爱丁堡出现的

and it must be the only celebrity sheep, Dolly.

这肯定是唯一的一只出名的绵羊了 多莉

So Dolly was made in Edinburgh,

多莉就是爱丁堡制造

and Dolly was an example

它是第一个克隆的哺乳动物

of the first cloning of a mammal

它是第一个克隆的哺乳动物

from an adult cell.

来自于一个小小的成年细胞

But I think the even more significant breakthrough

但是我认为更加重要的一项突破

for the purposes of our discussion today

同时也是今天我们讨论的基础

was made in 2006 by a Japanese scientist

是2006年一位日本科学家

called Yamanaka.

名为山中

And what Yamaka did,

他用了一种

in a fantastic form of scientific cookery,

令人称奇的科学方式将

was he showed that four ingredients,

四种成分如烹调般混在一起

just four ingredients,

仅仅四种

could effectively convert any cell, adult cell,

就能有效地转换任何一个细胞 任何成年细胞

into a master stem cell.

使之变成干细胞

And the significance of this is difficult to exaggerate,

这项研究意义之重大难以言喻

because what it means that from anybody in this room,

因为这就意味着在这间会议室的任何一个人

but particularly patients,

尤其是病人

you could now generate

可以生长出

a bespoke, personalized tissue repair kit.

一套私人定制 个性化的成套修复工具

Take a skin cell, make it a master pluripotent cell,

取一个皮肤细胞 将其培育成多功能细胞，

so you could then make those cells

这样便能生长出许多

that are relevant to their disease,

与疾病相关的细胞

both to study but potentially to treat.

可以用于研究也能用于未来的治疗

Now, the idea of that at medical school --

现在 医学院对此的看法

this is a recurring theme, isn't it, me and medical school? —

是觉得很荒谬

would have been ridiculous,

这是一个无限循环的主题 不是吗：我 医学院

but it's an absolute reality today.

但今时今日这是绝对的现实

And I see this as the cornerstone

我认为这是一个

of regeneration, repair and hope.

再生长 修复以及希望的转折点

And whilst we're on the theme of hope,

既然说到了希望的主题

for those of you who might have failed at school,

那些在学校表现欠佳的人

there's hope for you as well,

你们也应心存希望

because this is the school report of John Gerdon.

因为这是一篇约翰戈登的学校报告

["I believe he has ideas about becoming a scientist; on his present showing this is quite ridiculous."]

“我相信他有科学家的想法；但他呈现的东西很荒谬”

So they didn't think much of him then.

所以他们当时不是很看好他

But what you may not know is that he got the Nobel Prize for medicine

但是你可能不知道的是他获得了诺贝尔医学奖

just three months ago.

就在三个月前

So to return to the original problem,

再回来说说最先前的问题

what is the opportunity of these stem cells,

这些干细胞

or this disruptive technology,

或者是分裂技术能提出怎样的机遇

for repairing the damaged brain,

帮助修复受损大脑

which we call regenerative neurology?

发展再生长神经学？

I think there are two ways you can think about this:

我们可以从两个方面来看再生神经学：

as a fantastic 21st-century drug discovery tool,

它可以成为本世纪一个极佳的药品研发工具

and/or as a form of therapy.

以及/或者作为治疗的手段

So I want to tell you a little bit about both of those

我想再花一点时间说说

in the next few moments.

这两方面

Drug discovery in a dish is how people often

制药发现就是人们常常

talk about this.

讨论的话题

It's very simple: You take a patient with a disease,

很简单：有一个身患疾病的病人

let's say motor neuron disease,

比如说患了神经元疾病

you take a skin sample,

我们取一点他皮肤样本

you do the pluripotent reprogramming,

然后进行多功能重组

as I've already told you,

就像我先前说的那样

and you generate live motor nerve cells.

生长出新的神经元细胞

That's straightforward, because that's what

直观明了 因为这就是

pluripotent cells can do.

多功能细胞的强大之处

But crucially, you can then compare their behavior

但重要的是 我们能将病人的行为

to their equivalent but healthy counterparts,

与健康的人

ideally from an unaffected relative.

最好是他们健康的亲人进行比较

That way, you're matching for genetic variation.

这样 他们能为基因变体做配对

And that's exactly what we did here.

这就是我们的研究

This was a collaboration with colleagues:

这是全体同事的共同努力：

in London, Chris Shaw; in the U.S., Steve Finkbeiner and Tom Maniatis.

伦敦的肖克里斯 美国的芬克贝勒斯蒂夫和马力特斯汤姆

And what you're looking at, and this is amazing,

你所看到的 是很了不起的

these are living, growing, motor nerve cells

这些鲜活的 正在生长的运动神经元细胞

from a patient with motor neuron disease.

是来自于一名身患运动神经元疾病的病人

It happens to be an inherited form.

细胞处在遗传阶段的状态

I mean, just imagine that.

仔细想想吧

This would have been unimaginable 10 years ago.

这在10年之前是想都没法儿想的

So apart from seeing them grow and put out processes,

除了能够观察细胞的生长以及干预过程外

we can also engineer them so that they fluoresce,

我们还能设计细胞使其发出荧光

but crucially, we can then track their individual health

但是重要的是 我们能追踪单个细胞的健康情况

and compare the diseased motor nerve cells

并将患病的神经元细胞与健康细胞进行比较

to the healthy ones.

并将患病的神经元细胞与健康细胞进行比较

And when you do all that and put it together,

当我们将这些细胞放在一起时

you realize that the diseased ones,

我们发现患病细胞

which is represented in the red line,

就是由红色线代表的

are two and a half times more likely to die

相较健康细胞而言死亡的几率

than the healthy counterpart.

高达2.5倍

And the crucial point about this is that you then have

重要的一点是接下来我们

a fantastic assay to discover drugs,

能用神奇的试验来发现制药

because what would you ask of the drugs,

因为我们对药物的要求

and you could do this through a high-throughput

只需要通过高流通量

automated screening system,

自动化的筛选系统完成

you'd ask the drugs, give me one thing:

我们将要求制药者一件事

find me a drug that will bring the red line

发明一种药能把这条红线更加

closer to the blue line,

靠近这条蓝线

because that drug will be a high-value candidate

因为这样的药物是一种高价值的备份

that you could probably take direct to human trial

能直接用于人类实验

and almost bypass that bottleneck

并且能绕过在制药发现中

that I've told you about in drug discovery

以动物为模型的

with the animal models,

瓶颈问题

if that makes sense. It's fantastic.

如果可行 这将妙不可言

But I want to come back

但是我想再回头说说

to how you might use stem cells directly

我们如何能直接利用干细胞

to repair damage.

来修复大脑损伤

And again there are two ways to think about this,

同样要通过两方面来思考

and they're not mutually exclusive.

这两方面可以相通

The first, and I think in the long run

第一 我觉得长远来说

the one that will give us the biggest dividend,

能为我们带来巨大回报的

but it's not thought of that way just yet,

让我们以不同视角去看待问题的

is to think about those stem cells that are already

是这些干细胞已经

in your brain, and I've told you that.

存在于我们大脑中的事实 我已经说过了

All of us have stem cells in the brain,

我们的大脑中都有干细胞

even the diseased brain,

即使受损大脑中也有

and surely the smart way forward

当然明智的方法是

is to find ways that you can promote and activate

想办法去促进并且激活

those stem cells in your brain already

这些已经存在于大脑中的干细胞

to react and respond appropriately to damage

使之正确应对大脑损伤

to repair it.

将其修复

That will be the future.

这是未来的远景

There will be drugs that will do that.

未来会有具有这样疗效的药物

But the other way is to effectively parachute in cells,

另外一种办法是有效地

transplant them in,

移植这些细胞

to replace dying or lost cells, even in the brain.

让其代替死亡或消逝的细胞

And I want to tell you now an experiment,

我想跟你们说说一项实验

it's a clinical trial that we did,

这是我们做的一项临床试验

which recently completed,

刚结束不久

which is with colleagues in UCL,

是和在伦敦大学学院的同事一起做的

David Miller in particular.

尤其是米勒大卫

So this study was very simple.

这项研究其实很简单

We took patients with multiple sclerosis

我们选出患有多发性硬化症的患者

and asked a simple question:

问自己一个简单的问题：

Would stem cells from the bone marrow

来自于骨髓的干细胞

be protective of their nerves?

能保护他们的神经么？

So what we did was we took this bone marrow,

所以我们选取了这一骨髓细胞

grew up the stem cells in the lab,

在实验室培植出干细胞

and then injected them back into the vein.

再将其注射进血管里

I'm making this sound really simple.

我尽量将这一过程简化描述

It took five years off a lot of people, okay?

这花了我们整整五年时间

And it put gray hair on me

我头发都白了

and caused all kinds of issues.

期间尽是这样那样的问题

But conceptually, it's essentially simple.

但这一概念本质上还是很简单的

So we've given them into the vein, right?

于是我们把干细胞注射进了血管

So in order to measure whether this was successful or not,

为了测量我们成功与否

we measured the optic nerve

我们测量了视觉神经

as our outcome measure.

作为我们成果的测量

And that's a good thing to measure in M.S.,

这在多发性硬化症中很有效

because patients with M.S. sadly suffer

因为多发性硬化症的患者很不幸的

with problems with vision --

会出现视力问题——

loss of vision, unclear vision.

失明 视线模糊

And so we measured the size of the optic nerve

所以我们测量了视觉神经

using the scans with David Miller

通过对米勒大卫进行扫描

three times -- 12 months, six months,

总共三次——12个月前一次 6个月前一次

and before the infusion --

以及注射前一次——

and you can see the gently declining red line.

你们可以看到红线有轻微的下降

And that's telling you that the optic nerve is shrinking,

这就是说视觉神经正在减少

which makes sense, because their nerves are dying.

确实说得通 因为这一神经细胞正在死亡

We then gave the stem cell infusion

然后我们注射了干细胞

and repeated the measurement twice --

并且连续测量了两次——

three months and six months --

三个月一次及六个月一次——

and to our surprise, almost,

令我们吃惊的是

the line's gone up.

这条线上升了

That suggests that the intervention

这意味着这一干预

has been protective.

奏效了

I don't think myself that what's happened

我个人认为

is that those stem cells have made new myelin

这些干细胞并没有生长出新的髓磷脂

or new nerves.

或者新的神经

What I think they've done is they've promoted

我认为是促进了

the endogenous stem cells, or precursor cells,

内生的干细胞或者是前体细胞

to do their job, wake up, lay down new myelin.

唤醒了他们使之能覆盖新的髓磷脂

So this is a proof of concept.

研究证明了这一点

I'm very excited about that.

我对此十分激动

So I just want to end with the theme I began on,

最后结束时我想再提先前的主题

which was regeneration and hope.

即再生长以及希望

So here I've asked John

我又问了约翰

what his hopes are for the future.

他未来的希望是什么

John: I would hope that

约翰：我希望

sometime in the future

未来的某一天

through the research that you people are doing,

通过你们的研究

we can come up with a cure

我们的疾病得以治愈

so that people like me can lead a normal life.

像我这样的病人就能过正常的生活了

SC: I mean, that speaks volumes.

这已经说的很明白了

But I'd like to close by first of all thanking John --

在结束这次演讲时 我首先想先感谢约翰

thanking John for allowing me to share

使我能够与你们分享他的

his insights and these clips with you all.

见解以及这些片段

But I'd also like to add to John and to others

我想对约翰及其他人补充的是

that my own view is, I'm hopeful for the future.

我个人的想法是 我对未来充满希望

I do believe that the disruptive technologies

我相信这样的极具颠覆性的技术

like stem cells that I've tried to explain to you

例如我前面解释的干细胞一样

do offer very real hope.

确实给了我们希望

And I do think that the day that we might be able

我坚信我们能够

to repair the damaged brain

修复受损大脑的那一天

is sooner than we think.

一定会提早到来

Thank you.

谢谢

(Applause)

（掌声）