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I'm very pleased to be here today
譯者: Chih Ying (Naomi) Chuang 審譯者: Harry Chen
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,