to talk to you all about how we might repair

今天我感到非常開心來這裡，

the damaged brain,

要跟你們大家談： 「如何我們有可能修復

and I'm particularly excited by this field,

受損的大腦」

because as a neurologist myself,

這方面使我特別地感到振奮，

I believe that this offers one of the great ways

因為我身為一個神經學專家，

that we might be able to offer hope

我相信這提供了 一個最棒的辦法，

for patients who today live with devastating

讓我們也許有能力送上希望

and yet untreatable diseases of the brain.

給病人們， 那些今天活著帶有造成損傷、

So here's the problem.

尚未能治癒的大腦病變的人。

You can see here the picture of somebody's brain

問題就在這裡，

with Alzheimer's disease

你可以看到這是某人大腦的圖片，

next to a healthy brain,

是患有阿滋海默症的人。

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

旁邊還有健康的大腦圖片，

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

很明顯的是在患有 阿滋海默症的大腦中

And I could show you equivalent pictures

被紅線圈起來的是明顯的損傷---

from other disease: multiple sclerosis,

萎縮和傷疤。

motor neuron disease, Parkinson's disease,

我還可以讓你看更多同性質的照片，

even Huntington's disease,

來自其他大腦病變：多發性硬化症、

and they would all tell a similar story.

運動神經疾病、巴金森氏症、

And collectively these brain disorders represent

甚至還有亨丁頓氏症，

one of the major public health threats of our time.

而且它們都訴說著相似的故事，

And the numbers here are really rather staggering.

還有這些大腦失常集合性地代表

At any one time, there are 35 million people today

我們此生主要的一個公眾健康威脅。

living with one of these brain diseases,

況且這人數真的讓人傻眼，

and the annual cost globally

以今天而言有三千五百萬人，

is 700 billion dollars.

患有這些病變的其中一種，

I mean, just think about that.

而且年度的花費全球性來說

That's greater than one percent

是七千億美金。

of the global GDP.

就單單想一下那個金額，

And it gets worse,

那是遠大於百分之１

because all these numbers are rising

的全球國內生產毛額。

because these are by and large

而且還會變糟，

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

因為人數、花費等所有的數據 一直在上升中，

So the question we really need to ask ourselves is,

因為這些絕大部分是

why, given the devastating impact of these diseases

年齡相關疾病而我們正活得更長壽。

to the individual,

所以我們真正需要問我們自己的問題是

never mind the scale of the societal problem,

什麼原因使得破壞性影響的 這些大腦病變

why are there no effective treatments?

發生在個人身上？

Now in order to consider this,

先不要關心到後續 造成的社會問題的規模。

I first need to give you a crash course

為什麼沒有能成功的療法？

in how the brain works.

現在為了要認真思考這問題，

So in other words, I need to tell you

我必須先給你們上一堂速成課，

everything I learned at medical school.

有關大腦是如何運作。

(Laughter)

所以換句話說我必須告訴你們

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

我在醫學院裡學到的所有一切。

Okay? (Laughter)

(笑聲)

So the brain is terribly simple:

不過相信我！ 這預計不會花太久，

it's made up of four cells,

可以吧？

and two of them are shown here.

大腦組織真的再簡單不過，

There's the nerve cell,

它是由四種細胞組成的，

and then there's the myelinating cell,

這邊展示了其中的兩種，

or the insulating cell.

有神經細胞、

It's called oligodendrocyte.

再來是髓鞘細胞，

And when these four cells work together

或叫絕緣細胞。

in health and harmony,

這叫寡突膠細胞。

they create an extraordinary symphony of electrical activity,

當四種細胞一起運作，

and it is this electrical activity

是在健康跟和諧之下，

that underpins our ability to think, to emote,

它們像電流般的傳輸行為 譜了出色的交響曲，

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

而且正是這些像電流般 的傳輸行為，

But equally, each of these individual four cells

支持我們去思考、表達情緒、

alone or together, can go rogue or die,

記住、學習、移動、 感知等等的能力。

and when that happens, you get damage.

但同等地每一個這四種細胞

You get damaged wiring.

單獨或一起可能不受控制或者死掉，

You get disrupted connections.

當這情況發生時你就會受到傷害，

And that's evident here with the slower conduction.

你會發生大腦網絡損壞、

But ultimately, this damage will manifest

你會發生大腦連結中斷，

as disease, clearly.

這邊就是證據， 有著較慢的大腦傳輸。

And if the starting dying nerve cell

最終這種損壞將肯定地表示

is a motor nerve, for example,

是大腦病變。

you'll get motor neuron disease.

如果最先開始死掉的神經細胞，

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

例如是運動神經細胞

of what happens with motor neuron disease.

你就會有運動神經細胞病變。

So this is a patient of mine called John.

因此，我想要給你們 看一個真人實例，

John I saw just last week in the clinic.

患有運動神經細胞病變 會有甚麼事發生？

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

這位是我的一位病人叫約翰

that led to the initial diagnosis

我才在上個星期的門診看過約翰，

of motor neuron disease.

我請約翰來告訴我們 有關他當時有甚麼毛病，

John: I was diagnosed in October in 2011,

造成之後首次診斷 是運動神經細胞病變。

and the main problem was a breathing problem,

我在2011年十月時就診的，

difficulty breathing.

(吃力呼吸)

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

當時主要的問題是有關呼吸方面，

was that difficulty with breathing

呼吸困難。

led eventually to the diagnosis

我不知道你是否全部聽清楚了， 約翰想告訴我們

of motor neuron disease.

是呼吸的時候會有困難，

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

導致最後的診斷出

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

運動神經細胞病變。

his current predicament.

約翰從那次診斷到現在 已過了18個月，

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

我現在請他來告訴我們關於

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

他目前的困境。

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

我現在變得呼吸更吃力、

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

我的手、上肢、下肢變得無力，

most of the time.

所以基本上我大部分時間都 坐在輪椅裡。

So what these two clips show

約翰告訴我們他是坐著輪椅

is not just the devastating consequence of the disease,

在大部分時間裡。

but they also tell us something about

所以這兩段短片所要表達的

the shocking pace of the disease,

不只是有關大腦病變的 嚴重傷害性的後果，

because in just 18 months,

而它們也告訴我們有關

a fit adult man has been rendered

病變驚人的惡化速度，

wheelchair- and respirator-dependent.

因為只是在18個月之內，

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

一個健全的成年男人已經給送上

brother or friend.

了輪椅而且要依靠呼吸器。

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

讓我們正視它， 約翰有可能是任何人的父親、

But what happens when that myelin cell dies?

兄弟或朋友。

You get multiple sclerosis.

這就是當運動神經細胞 死亡時會發生的事。

So the scan on your left

那髓鞘細胞死亡時又會如何？

is an illustration of the brain,

你將患有多發性硬化症。

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

所以在你左手邊的掃描

and superimposed upon which

正是一張大腦的圖片，

are areas of damage.

而且它也是大腦連結路徑的地圖，

We call them lesions of demyelination.

上面又被標記出的是

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

大腦受損的地方，

So I know what you're thinking here.

我們稱作「去髓鞘損傷」，

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

不過它們壞掉了、還有是白色的。

and said he's going to talk about hope,

我知道你在想什麼，

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

你正在想，「我的天哪！ 這傢伙上台來，

and depressing tale."

說他想談的是希望，

I've told you these diseases are terrible.

所有他做的事就是說了再無望不過

They're devastating, numbers are rising,

以及令人沮喪的故事。」

the costs are ridiculous, and worst of all,

我剛跟你說過這些病變是可怕的。

we have no treatment. Where's the hope?

它們是傷害性的、數字一直上升中的、

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

費用是太離譜的，且最糟糕的是

And there's hope in this next section,

我們沒有治療方法，希望在哪裡呢？

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

你們知道嗎我認為是有希望的，

because what it illustrates

而且希望就在旁邊那張剖面圖裡，

is, amazingly, the brain can repair itself.

是某位患有多發性硬化症病人 的大腦剖面圖，

It just doesn't do it well enough.

因為令人驚訝地是它說明了，

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

大腦能夠自癒，

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

它只是自癒做得還不夠好。

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

有兩件事我要告訴你。

But crucially, the area that's ringed red

首先，是患有多發性硬化症的 這個病人大腦有損傷。

highlights an area that is pale blue.

再來一次就是這些白色區塊的一塊。

But that area that is pale blue was once white.

但很重要地，是這個被紅色圈起來的地方

So it was damaged. It's now repaired.

註記了一個淡藍色的區域，

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

但是那個淡藍色的區域原本是白色的。

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

就是說它曾經是受損的， 現在已經修復了。

This is spontaneous repair.

再澄清一些，這不是醫生們造成的。

It's amazing and it's occurred

這是醫生以外的因素， 不是醫生們造成的。

because there are stem cells in the brain, even,

這是自主性的修復。

which can enable new myelin, new insulation,

這很令人驚奇的而且它發生了

to be laid down over the damaged nerves.

就是因為大腦中有幹細胞，

And this observation is important for two reasons.

甚至可以使新的髓鞘細胞、絕緣體

The first is it challenges one of the orthodoxies

包覆在受損的神經上。

that we learnt at medical school,

這個觀察之所以重要有兩個原因，

or at least I did, admittedly last century,

第一、是它質疑了一個正統學說

which is that the brain doesn't repair itself,

就是我們當初在醫學院裡學到的，

unlike, say, the bone or the liver.

起碼是我曾學習到， 誠然地是在上個世紀時，

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

就是大腦不能自癒，

And the second thing it does,

不像好比說是骨頭或肝臟。

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

不過實際上它可以自癒， 只是它自癒得還不夠好。

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

它做的第二件事，

to know what to do here.

它給了我們一個清楚的方向 去找出新的療法，

You simply need to find ways of promoting

我說的是你不必是極聰明的人，

the endogenous, spontaneous repair that occurs anyway.

去知道這裡要做甚麼。

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

你僅需要找出方法來促使

for some time, as we have,

內生性、自主性的修復 無論如何都能啟動。

why do we not have those treatments?

問題是如果我們已經知道這些

And that in part reflects the complexity

有一段時間了，

of drug development.

為什麼我們還沒有治療那 些大腦損傷的方法？

Now, drug development you might think of

那有一部分原因反映出藥品開發

as a rather expensive but risky bet,

的複雜性。

and the odds of this bet are roughly this:

現在藥品開發你可能會想到

they're 10,000 to one against,

既昂貴又有風險的賭博，

because you need to screen about 10,000 compounds

而這賭博的實現機率大概是

to find that one potential winner.

萬分之一，

And then you need to spend 15 years

因為你需要測試約ㄧ萬種配方，

and spend over a billion dollars,

去找出那一個有可能成功的正解。

and even then, you may not have a winner.

接著你需要花15年的時間，

So the question for us is,

以及支出超過10億美元，

can you change the rules of the game

甚至到後來你並沒有正解。

and can you shorten the odds?

所以我們該問的問題是，

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

你可以改變遊戲規則嗎？

where is the bottleneck in this drug discovery?

你可以縮短找到正解的時間嗎？

And one of the bottlenecks is early in drug discovery.

為了達到這個目的你必須去想，

All that screening occurs in animal models.

藥品開發的瓶頸在哪？

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

其中一個瓶頸在藥品開發的初期，

to borrow from Alexander Pope.

所有的測試都發生在動物實驗體上。

So the question is, can we study these diseases

不過我們知道 正確的研究人類要用真人，

using human material?

我借用亞歷山大．波普的話。

And of course, absolutely we can.

所以問題是：我們能否研究這些疾病

We can use stem cells,

使用真人？

and specifically we can use human stem cells.

當然，我們絕對可以。

And human stem cells are these extraordinary

我們可以用幹細胞，

but simple cells that can do two things:

尤其是人類的幹細胞，

they can self-renew or make more of themselves,

人類的幹細胞是很不一樣

but they can also become specialized

但又簡單的細胞，可以做到兩件事情：

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

它們懂得再生 或是製造出更多幹細胞，

maybe even the motor nerve cell

它們可以特化為

or the myelin cell.

骨頭、肝臟，或者很關鍵地 －神經的細胞，

And the challenge has long been,

可能甚至是運動神經細胞，

can we harness the power,

或是髓鞘細胞。

the undoubted power of these stem cells

而存在了很久的挑戰是

in order to realize their promise

我們是否能獲取這份力量，

for regenerative neurology?

這些幹細胞無庸置疑的力量，

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

來實現它們為

is because there have been several major discoveries

再生神經學帶來的好消息？

in the last 10, 20 years.

我想我們現在可以， 而我們可以的理由

One of them was here in Edinburgh,

是因為在過去的10~20年間

and it must be the only celebrity sheep, Dolly.

有很多重大的發現。

So Dolly was made in Edinburgh,

其中之一就發生在愛丁堡這裡，

and Dolly was an example

而牠必定是唯一的名羊 ～桃麗。

of the first cloning of a mammal

桃麗是在愛丁堡製造的，

from an adult cell.

桃麗也是一個例子

But I think the even more significant breakthrough

第一個複製哺乳類

for the purposes of our discussion today

取樣自成羊細胞。

was made in 2006 by a Japanese scientist

但我認為更重大的突破，

called Yamanaka.

與我們今天的討論目的相關的

And what Yamaka did,

是2006年由一位 日本的科學家做出的，

in a fantastic form of scientific cookery,

是山中伸彌 (Yamanaka) 。

was he showed that four ingredients,

而山中伸彌所做的，

just four ingredients,

在一個神奇的科學大熔爐，

could effectively convert any cell, adult cell,

是他指出四種成分，

into a master stem cell.

只要四種成分，

And the significance of this is difficult to exaggerate,

能夠成功地轉換任何細胞、成人細胞

because what it means that from anybody in this room,

成為主要的幹細胞。

but particularly patients,

而這個突破的重大性 高到不能再誇大，

you could now generate

因為它表示從在這房間的每個人

a bespoke, personalized tissue repair kit.

特別是病人，

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

你可以產生

so you could then make those cells

客製化、個人化的細胞修復包。

that are relevant to their disease,

取下皮膚細胞把它變成 主要的多功能幹細胞，

both to study but potentially to treat.

接著你可以用那些細胞，

Now, the idea of that at medical school --

與大腦病變有關連的細胞

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

既可用於研究，又可用於治療。

would have been ridiculous,

這個想法在醫學院

but it's an absolute reality today.

不是一直不斷上演的主題嗎？ 對我和醫學院而言

And I see this as the cornerstone

可以說是再荒唐不過的。

of regeneration, repair and hope.

但在今天它絕對是事實。

And whilst we're on the theme of hope,

我則把它視為

for those of you who might have failed at school,

重建、修復與希望的基礎。

there's hope for you as well,

既然我們在談"希望"這個主題，

because this is the school report of John Gerdon.

對你們也許曾在學校被當掉的人而言，

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

你們一樣是有希望的。

So they didn't think much of him then.

因為這是約翰．格登的成績報告書：

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

「我相信他有想要成為科學家這想法； 以他現在的表現來說是相當荒謬的。」

just three months ago.

所以他們之後並不常想起他，

So to return to the original problem,

不過你可能不知道 他得了諾貝爾醫學獎

what is the opportunity of these stem cells,

就在三個月之前。

or this disruptive technology,

讓我們回到原來的問題，

for repairing the damaged brain,

這些幹細胞成功的機會在哪裡？

which we call regenerative neurology?

或者這顛覆性性科學

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

用來療癒受損的大腦，

as a fantastic 21st-century drug discovery tool,

我們現在稱做重建神經學。

and/or as a form of therapy.

我認為你有兩個方向來看它：

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

當它是神奇的21世紀藥品開發的工具

in the next few moments.

或者是一種治療手段。

Drug discovery in a dish is how people often