FrancisCollins_2012P[弗朗西斯.柯林斯][我们需要更好地药物——就是现在].pdf

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1、www.XiYuS锡育软件So let me ask for a show of hands.請用舉手的方式回答我。00:13How many people here are over the age of 48?多少人超過48歲？00:15Well,there do seem to be a few.看來並不多。00:19Well,congratulations,because if you look at this particularslide of U.S.life expectancy,you are now in excess of theaverage life span of

2、somebody who was born in 1900.恭喜大家,因為如果當你看到這張幻燈片上美國人的預期壽命,現在各位的壽命都超過 1900 年出生的一些人。00:22But look what happened in the course of that century.但看看在這個世紀裏發生了什麼事。00:34If you follow that curve,youll see that it starts way downthere.如果各位沿著這條曲線,可以看到它從這下降了。00:37Theres that dip there for the 1918 flu.那就是因爲 191

3、8 年大流感。00:42And here we are at 2010,average life expectancy of a childborn today,age 79,and we are not done yet.這是 2010 年的數據,這一年出生的小孩,預估平均壽命為 79 歲,而且還會繼續增長。00:44Now,thats the good news.目前,這是個好消息。00:52But theres still a lot of work to do.但還有很多工作要做。00:53So,for instance,if you ask,how many diseases do

4、we nowknow the exact molecular basis?舉例來說,如果你問,我們現在到底知道多少疾病的精確的分子基礎？00:55Turns out its about 4,000,which is pretty amazing,becausemost of those molecular discoveries have just happened inthe last little while.說穿了大概就是 4,000 種,這是非常了不起的,而且發現這些分子大部分都是 最近前發生的。01:01expectancy:n.期望,期待 in the course of:在过程中

5、;在期间 flu:n.流感 molecular:adj.化学分子的;由分子组成的Its exciting to see that in terms of what weve learned,buthow many of those 4,000 diseases now have treatmentsavailable?從已知的觀點,很興奮可以看到這樣的結果,但是4000 種疾病中,有多少疾病 現在有治療方法？01:10Only about 250.大概祇有 250 種。01:17So we have this huge challenge,this huge gap.所以我們面對著非常巨大的挑

6、戰,巨大的差距。01:19You would think this wouldnt be too hard,that we wouldsimply have the ability to take this fundamental informationthat were learning about how it is that basic biology teachesus about the causes of disease and build a bridge across thisyawning gap between what weve learned about basicsc

7、ience and its application,您可能會想這件事也不會太困難,我們很容易就能獲取基本資訊,關於基礎生物學是如何告訴我們的關於疾病的生成原因 以及在一條大壕溝的上面蓋一座橋樑,一邊是我們學到的基礎科學,另外一邊是它的應用。01:22a bridge that would look maybe something like this,whereyoud have to put together a nice shiny way to get from oneside to the other.一座橋,看起來也許像這樣,我們必須建一條優良的康莊大道 從一側連結到另一側。01:41

8、Well,wouldnt it be nice if it was that easy?嗯,是不是如果這麼簡單就太好了?01:51Unfortunately,its not.不幸的是,事與願違。01:54In reality,trying to go from fundamental knowledge to itsapplication is more like this.在現實中,試圖從基礎知識 走向該知識的實際應用,更像是這樣。01:56in terms of:依据;按照;在方面;以措词 treatments:n.临床治疗(treatment的复数);处理 yawning:adj.打哈欠

9、的,张着大嘴的/n.打呵欠/v.打哈欠(yawn的ing形式)put together:.放在一起;组合;装配 shiny:adj.有光泽的,擦亮的;闪耀的;晴朗的;磨损的There are no shiny bridges.沒有閃亮的橋樑。02:01You sort of place your bets.如同你在下賭注。02:03Maybe youve got a swimmer and a rowboat and a sailboatand a tugboat and you set them off on their way,and therains come and the light

10、ning flashes,and oh my gosh,thereare sharks in the water and the swimmer gets into trouble,and,uh oh,the swimmer drowned and the sailboatcapsized,and that tugboat,well,it hit the rocks,and maybeif youre lucky,somebody gets across.也許你會得到一位泳將和划艇 一艘拖船和一艘帆船 然後你開始給他們方向,開始下雨、雷電交加唉呦喂呀,水中還有鯊魚 你的泳將陷入大麻煩,喔哦,你

11、的泳將溺水了 帆船翻船了,這艘拖船,撞到大石頭,如果你幸運的話,剛好有人要過去。02:04Well,what does this really look like?事實上這樣看起來像什麼？02:25Well,what is it to make a therapeutic,anyway?到底什麼東西可以有療效?02:27TED演讲者：Francis Collins|弗朗西斯.柯林斯演讲标题：Francis Collins:We need better drugs-now|我们需要更好地药物就是现在内容概要：A key player in the US.new brain-mapping pro

12、ject,Francis Collins is director of theNational Institutes of Health.如今我们知道4000种疾病的分子成因，但只有250种有相应的治疗药物。为何需要如此之久的时间?遗传学家和医生弗朗西斯解释了研发系统化药物的必要性，甚至对罕见和复杂疾病也是如此。他提供了一些解决方案，例如老药新用。Whats a drug?A drug is made up of a small molecule ofhydrogen,carbon,oxygen,nitrogen,and a few other atomsall cobbled togethe

13、r in a shape,and its those shapes thatdetermine whether,in fact,that particular drug is going tohit its target.藥是什麼?藥是由 氫分子、碳分子、氧分子、氮分子、和其它幾個原子 組合而成的特定形狀,正是靠這些形狀,事實上,決定是否某種特定的藥物可擊中目標。02:29swimmer:n.游泳者 rowboat:n.划艇;小船 sailboat:n.帆船 tugboat:n.拖船(等于towboat或tug)flashes:n.闪光灯(flash的复数形式);光芒;披峰/v.闪光;反射(f

14、lash的单三形式)drowned:v.淹死(drown的过去分词);淹没/adj.淹死的;水淹的/n.血本无归者;被套牢者 capsized:v.倾覆(capsize的过去分词);翻船;覆没/adj.翻覆的 therapeutic:adj.治疗的;治疗学的;有益于健康的/n.治疗剂;治疗学家 made up of:由组成,由构成 molecule:n.化学分子;微小颗粒,微粒 atoms:n.物原子(atom的复数)cobbled:adj.铺有鹅卵石的/v.铺鹅卵石(cobbled的过去式和过去分词)Is it going to land where its supposed to?它會到達

15、它應該去的地方嗎?02:45So look at this picture here-a lot of shapes dancing aroundfor you.看看這張照片-各位的周遭都有很多這種形狀在跳舞。02:47Now what you need to do,if youre trying to develop a newtreatment for autism or Alzheimers disease or cancer is tofind the right shape in that mix that will ultimately providebenefit and wil

16、l be safe.現在你需要做什麼,如果你想要探索 自閉症的新治療法 或阿茲海默症、或癌症 是在混和之中找到正確的形狀,最終會帶來好處,而且很安全。02:50And when you look at what happens to that pipeline,youstart out maybe with thousands,tens of thousands ofcompounds.當你觀察這些管線,你也許從成千上萬,上億的化合物開始。03:01You weed down through various steps that cause many ofthese to fail.你釐清各個

17、的步驟 這導致許多失敗。03:07Ultimately,maybe you can run a clinical trial with four or fiveof these,and if all goes well,14 years after you started,youwill get one approval.最終,也許您可以對其中的 45 項做臨床試驗,如果一切順利,在你開始14 年後,你得到一個批准。03:11And it will cost you upwards of a billion dollars for that onesuccess.它將花費超過 10 億美金 就

18、為了一次成功。03:19So we have to look at this pipeline the way an engineerwould,and say,How can we do better?所以我們必須用一種工程師的思維看看這條管線,並說,可以做得更好嗎?03:23autism:n.心理内科孤独症;自我中心主义 start out:出发;着手进行 compounds:n.混合物,化合物;大院(compound的复数形式)weed:vt.除草;铲除/n.杂草,野草;菸草/vi.除草 clinical:adj.临床的；诊所的 upwards:adv.向上;在上部;向上游And tha

19、ts the main theme of what I want to say to you thismorning.這就是今天早上要對各位說的主題。03:28How can we make this go faster?如何讓整件事進行得更快?03:30How can we make it more successful?我們如何讓它更成功？03:32Well,let me tell you about a few examples where this hasactually worked.讓我告訴你幾個例子 實際有效的例子。03:35One that has just happened

20、in the last few months is thesuccessful approval of a drug for cystic fibrosis.一個案例是幾個月前才發生的事情 一項針對 囊狀纖維化 的藥物成功取得審批。03:39But its taken a long time to get there.但是已經花了很長一段時間才得到。03:45Cystic fibrosis had its molecular cause discovered in 1989 bymy group working with another group in Toronto,discovering

21、 what the mutation was in a particular gene onchromosome 7.囊狀纖維化 已於1989 年發現其分子層的成因。經由我的團隊與位於多倫多的團隊一起合作 發現一個特定的基因突變 在7 號染色體。03:47That picture you see there?看到的那幅畫了嗎？03:58Here it is.Thats the same kid.是的。這就是同一的孩子。04:00Thats Danny Bessette,23 years later,because this is the year,and its also the year w

22、here Danny got married,where wehave,for the first time,the approval by the FDA他叫丹尼班賽特,23 年之後,就是這一年 也是在丹尼結婚的一年 我們第一次通過 FDA 批准04:02of a drug that precisely targets the defect in cystic fibrosisbased upon all this molecular understanding.一種藥物可精確地修復 囊狀纖維化 的缺陷 基於所有對分子的認識的基礎上。04:12cystic:adj.囊的;膀胱的,解剖胆囊的;

23、胞囊的 fibrosis:n.医纤维化,病理纤维变性 mutation:n.遗突变;变化;元音变化chromosome:n.遗细胞染料染色体(形容词chromosomal,副词chromosomally)Thats the good news.這是個好消息。04:18The bad news is,this drug doesnt actually treat all cases ofcystic fibrosis,and it wont work for Danny,and were stillwaiting for that next generation to help him.壞消息是

24、,這種藥物並不真的可以治療所有的 囊狀纖維化 對丹尼就無效,然而我們仍然在等待 希望下一代可以幫助到他。04:19But it took 23 years to get this far.Thats too long.但歷經了 23 年才到這邊。實在太長太久。04:27How do we go faster?我們如何加速?04:31Well,one way to go faster is to take advantage oftechnology,and a very important technology that wedepend on for all of this is the h

25、uman genome,the ability tobe able to look at a chromosome,to unzip it,to pull out all嗯,一種加速方式是利用科技,一種我們非常看重的技術 適用於全人類的基因組,能够看到一對染色體,解開它,並拔出所有的 DNA,04:32be able to look at a chromosome,to unzip it,to pull out allthe DNA,www.XiYuS锡育软件and to be able to then read out the letters in that DNA code,the As,

26、Cs,Gs and Ts that are our instruction book and theinstruction book for all living things,and the cost of doingthis,然後能夠解讀該 DNA 代碼中的密码子 A、C、G的和 T 的 這是我們人類的指令書和一切生物的建構組成指導書,做到這一點的成本04:45which used to be in the hundreds of millions of dollars,has inthe course of the last 10 years fallen faster than Moo

27、res Law,down to the point where it is less than 10,000 dollars todayto have your genome sequenced,or mine,and were headedfor the$1,000 genome fairly soon.曾經需要好幾億美元 在過去 10 年中 下降的速度已超越摩爾定律,今天做一份你我的基因體定序已經低於一萬美元 我們正快速朝向1,000 美元基因體定序前進。04:55genome:n.基因组;染色体组 unzip:vi.拉开拉链;释放/vt.拉开 pull out:离开,撤离;拔出;渡过难关

28、;恢复健康;折叠的大张插页;飞机进场重新飞起 sequenced:数计序列Well,thats exciting.嗯,真令人興奮。05:10How does that play out in terms of application to a disease?應用於疾病的觀點,這件事是如何演變的?05:11I want to tell you about another disorder.我要告訴你另一個障礙。05:15This one is a disorder which is quite rare.這是非常罕見的一種紊亂。05:17Its called Hutchinson-Gilfor

29、d progeria,and it is the mostdramatic form of premature aging.它被稱為哈欽森-吉爾福德（早衰症）,它是最具戲劇性的過早老化現象。05:19Only about one in every four million kids has this disease,and in a simple way,what happens is,because of a mutationin a particular gene,a protein is made thats toxic to the celland it causes these in

30、dividuals to age at about seven timesthe normal rate.大約每個 400 萬孩子中只有 1位有這種疾病,一種簡單的方式發生,發生的情況是,因為在一個特定的基因突變 產生一種對細胞有毒的蛋白質 造成這些人老化 老化的速度比一般人快 7 倍。05:26Let me show you a video of what that does to the cell.透過一段影片說明這個突變對細胞做了什麼事。05:43The normal cell,if you looked at it under the microscope,would have a n

31、ucleus sitting in the middle of the cell,whichis nice and round and smooth in its boundaries and it lookskind of like that.正常的細胞,如果你在顯微鏡下看它是這樣 會有一個核心在細胞中央,邊緣是是漂亮、圓潤、平滑 和它看上去有點像。05:46A progeria cell,on the other hand,because of this toxicprotein called progerin,has these lumps and bumps in it.另一方面,早衰

32、症細胞 因為這種有毒蛋白質,稱為早衰蛋白(progerin),有這些腫塊與凹凸不平整。05:58play out:结束;放出;用完;做完 toxic:adj.有毒的；中毒的 on the other hand:另一方面 lumps:n.肿块(lump的复数);金丝鸟病;块煤/v.结块;成团;笨重地行走(lump的第三人称单数)bumps:碰撞(bump的第三人称单数)/碰撞(bump的复数)So what we would like to do after discovering this back in2003 is to come up with a way to try to corre

33、ct that.發見這件事後,最想做的事 早在 2003 年 就是找出修正它的方法。06:05Well again,by knowing something about the molecularpathways,it was possible to pick one of those many,manycompounds that might have been useful and try it out.同樣,透過瞭解分子途徑,是有可能 從許多化合物中找出有用的一個 然後試試看。06:13In an experiment done in cell culture and shown her

34、e in acartoon,if you take that particular compound and you add itto that cell that has progeria,and you watch to see whathappened,in just 72 hours,that cell becomes,for allpurposes that we can determine,almost like a normal cell.培養細胞時做的一個實驗 在此以動畫方式秀出來,如果把特定化合物 將其加到具有早衰症的細胞,你看發生什麼事,在短短 72 小時內,那個細胞變成

35、可由我們控制的所有目標。幾乎就是一個正常細胞。06:22Well that was exciting,but would it actually work in a realhuman being?真令人興奮,但在實際人體中是否也有效?06:42This has led,in the space of only four years from the time thegene was discovered to the start of a clinical trial,to a test ofthat very compound.僅四年的空間裡 從發現基因到臨床實驗測試 到測試那個非常複合物

36、。06:46And the kids that you see here all volunteered to be part ofthis,28 of them,and you can see as soon as the picturecomes up that they are in fact a remarkable group of youngpeople all afflicted by this disease,all looking quite similarto each other.然後看到這些孩子 全部都是自願參加的,一共有28位,从照片上可以看出 他們事實上是一群非常突

37、出的年輕人。他们都患有這種疾病,每個人都很相似。06:56come up with:提出;想出;赶上 pathways:n.小路;小径(pathway的复数)afflicted:折磨 similar to:与相似;和相同And instead of telling you more about it,Im going to inviteone of them,Sam Berns from Boston,whos here thismorning,to come up on the stage and tell us about hisexperience as a child affected

38、 with progeria.與其告訴你更多資訊,不如邀請其中之一,從波士頓來的 山姆 伯恩斯 他早上來到這裡,站上這舞台 告訴我們他的經歷。身為早衰症的患童。07:12Sam is 15 years old.His parents,Scott Berns and LeslieGordon,both physicians,are here with us this morning aswell.山姆現在15 歲。他的父母,斯科特 伯恩斯和萊斯利 戈登 和兩位醫生早上也都和我們在一起。07:24Sam,please have a seat.山姆,請坐。07:30(Applause)So Sam,

39、why dont you tell these folks what itslike being affected with this condition called progeria?（掌聲）山姆,你何不告訴大家 身受早衰症所苦的的感覺是什麼?07:33Sam Burns:Well,progeria limits me in some ways.山姆伯恩斯:嗯,早衰症限制我某些發展。07:45I cannot play sports or do physical activities,but I have beenable to take interest in things that p

40、rogeria,luckily,does notlimit.我不能運動或肢體活動 但是我一直可以對事物感到興趣 幸運的是,早衰症並不侷限我的興趣。07:49But when there is something that I really do want to do thatprogeria gets in the way of,like marching band or umpiring,we always find a way to do it,and that just shows thatprogeria isnt in control of my life.但當我真正想做某件事 早衰

41、症有點像鼓號樂隊般介入 或像主審,我們總是找方法去做,只是要說明早衰症並沒有控制我的人生。07:59on the stage:在舞台上;现阶段;当演员 physicians:n.内科内科医生(physician的复数)in the way:妨碍;挡道 marching:adj.行军的;步进式的/v.行军;进军(march的ing形式)(Applause)Francis Collins:So what would you like to say toresearchers here in the auditorium and others listening tothis?（掌聲）法蘭西斯 柯林

42、斯:所以,您想要對研究人員說什麼 在這個禮堂及所有聆聽的人？08:12What would you say to them both about research onprogeria and maybe about other conditions as well?你會針對早衰症的研究說什麼 也許其他有關的狀況說時麼?08:19SB:Well,research on progeria has come so far in less than 15years,and that just shows the drive that researchers can haveto get this f

43、ar,and it really means a lot to myself and otherkids with progeria,and it shows that if that drive exists,anybody can cure any disease,SB:嗯,研究早衰症至今 不少於15年,只要研究者有一條路 撐到目前為止,有非常的意義 對我自己和所有早衰症的孩子們,只要還有一條路,任何人都可以治癒任何疾病,08:23and hopefully progeria can be cured in the near future,andso we can eliminate th

44、ose 4,000 diseases that Francis wastalking about.期望早衰症在不久的將來是可以被治癒的,因此,我們可以消除這 4,000 種疾病 這就是法蘭西斯所言。08:45FC:Excellent.So Sam took the day off from school today tobe here,and he is?(Applause)-He is,by the way,astraight-A+student in the ninth grade in his school inBoston.FC:很棒。山姆今天向學校請假一天。來到這裡,他是-(掌聲)-

45、順便說明,他是成绩一直優等的九年級學生 在他的學校在波士頓。08:56Please join me in thanking and welcoming Sam.請和我一起感謝並歡迎山姆。09:10SB:Thank you very much.FC:Well done.Well done,buddy.SB:非常感謝你。FC:非常好。非常好,朋友。09:12(Applause)So I just want to say a couple more things aboutthat particular story,and then try to generalize how could wehav

46、e stories of success all over the place for these diseases,asSam says,these 4,000 that are waiting for answers.（掌聲）我想要再講一、兩件事,關於特別的故事,進而希望推廣 我們如何能有成功的故事呢 如同山姆所說,這些疾病片佈各地,這4,000種疾病在等待解答。09:16auditorium:n.礼堂,会堂;观众席 buddy:n.伙伴,好朋友;密友;小男孩/vi.做好朋友,交朋友 generalize:vt.概括;推广;使.一般化/vi.形成概念You might have notic

47、ed that the drug that is now in clinicaltrial for progeria is not a drug that was designed for that.您可能已經注意到這個藥物 正在做早衰症的臨床試驗 並不是為了這個目的而製成的藥。09:42Its such a rare disease,it would be hard for a company tojustify spending hundreds of millions of dollars to generate adrug.這麼罕見的疾病,很難找到公司 願意花上億美元研發藥物。09:4

48、9This is a drug that was developed for cancer.這是一種治療癌症的藥物。09:55Turned out,it didnt work very well for cancer,but it hasexactly the right properties,the right shape,to work forprogeria,and thats whats happened.事實證明,這藥對癌症沒有很有效,但是這藥有完全相同的屬性與形狀 對早衰症有效,就是這麼回事。09:57Wouldnt it be great if we could do that

49、moresystematically?如果我們能更有系統地這樣做,不是很棒嗎？10:05Could we,in fact,encourage all the companies that are outthere that have drugs in their freezers that are known to besafe in humans but have never actually succeeded in terms ofbeing effective for the treatments they were tried for?事實上,我們可以鼓勵所有市場上的公司 公司冷凍櫃

50、中的藥物 只要是對人類是安全的 但從來沒有真正成功地 有效治療他們原來被試驗的目的？10:08Now were learning about all these new molecular pathways-some of those could be repositioned or repurposed,orwhatever word you want to use,for new applications,basically teaching old drugs new tricks.現在我們正在學習這些新的分子途徑-其中一些這種藥物可以被重新定位或改變用途,若用你想要用的字眼用在新的應用