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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,

  • 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

    我想再多告訴你一些有關這兩者的事

  • talk about this.

    就在接下來的幾分鐘,

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

    在培養皿裡做藥品研究是人們

  • let's say motor neuron disease,

    最常想到的,