BBC地平線系列之《藥物依賴》課件

1、BBC地平線系列之藥物依賴245第1集:人的一生要吃四千粒藥Over the course of your lifetime, 在你的一生中you're likely to be prescribed more than 14,000 pills. 醫(yī)生可能給你開了超過一萬四千顆藥丸Tiny little spheres of 這種小小的粉末壓片crushed powder with almost magical effects, 有著魔法般的功效pills that will possibly save 藥物可以拯救生命and extend your life by decades.

2、 并將壽命延長數(shù)十年Any medicine actually is a miracle. 實際上 任何藥物都是一種奇跡If you really think about what a medicine does, 只要你想想藥物的工作原理that you can design a small chemical 人居然能研制出一種化學藥品to interfere with a biological process to alter disease. 調(diào)控生物進程 進而治療疾病.I mean, it is just astonishing that you ever get there. 我們能

3、做到這一點真的令人嗔目結舌These miraculous pills 這些神奇藥物得以出現(xiàn)often owe as much to serendipity as science. 所需的運氣與研究并重We started with a drug that we hoped would be effective in angina 我們研制這種藥的初衷 是為了治療心絞痛and we ended up with a medicine 最后卻發(fā)現(xiàn)這種藥物that was highly effective in erectile dysfunction. 對治療陽痿非常有效This accident

4、al nature of drug discovery means little is known 這種藥物發(fā)現(xiàn)的偶然性表明about what they can do until we all take them. 在服用藥物前我們對它知之甚少In many ways you learn as much about 即便投放市場之后your medicine after it's launched as you knew before. 你對藥物許多方面的了解也并無增加246第2集:依靠藥物過日子Our relationship with pills 我們和藥物的聯(lián)系starts f

5、rom the very beginning of our lives, 從生命的最初開始from the medicines handed to us by our parents. 從父母遞給我們藥片時就開始了I used to get so upset having to 以前必須吃這些止痛藥take these pain killers because I didn't want to, 總讓我很煩惱 因為我不想吃so my mum, I was probably about five, 我當時大概五歲 所以我媽and my mum used to snap them in h

6、alf 把它們掰成兩半and tip the actual medication into orange squash for me. 把藥倒到橙汁里給我喝My mum gives me my tablets every day. 我媽媽每天都給我吃藥As we grow up, we begin to pop pills for everything. 隨著我們長大 我們開始凡事依賴藥物There are the antibiotics we take to fight off disease, 我們服用抗生素 去抗擊疾病more than one course every two year

7、s of our lives. 每兩年還要吃不止一個療程The 28,000 pain killers we each take 有28000種止痛藥供人挑選to make us feel better. 用于減少痛苦Pills to stop us having babies. 還有幫人避孕的藥片I actually got pregnant on the pill. 我其實是靠吃藥幫助才懷孕的So. 所以Medicines to carry us through middle age. 幫人度過中年綜合癥的藥物Statins. 抑制素Even tablets to extend our y

8、outh 甚至還有幫我們延緩衰老and improve our performance in bed. 提升床上戰(zhàn)斗力的藥物247第3集:葛蘭素史克This is a temple to modern science - 這是現(xiàn)代科學的一座神殿the pharmaceutical labs at GSK. 葛蘭素史克公司的制藥實驗室But modern drug discovery relies 但現(xiàn)代藥品的發(fā)現(xiàn)more on an automated lottery than careful design. 更依賴于運氣而不是精心的設計This store of chemical compo

9、unds 這個化合物倉庫is the company's crown jewels. 就是公司的核心所在This is where their new drugs come from. 這就是新藥物的來源地In here is a library of 這里是超過兩百萬的over two million nameless chemical compounds. 未命名化合物的倉庫The scientists know very little about them. 科學家們對它們了解甚少They could be highly toxic, 它們可能有劇毒or they could b

10、e harbouring a life-saving drug. 也可能是治病救人的良藥It really is trying to find a needle in a haystack. 這實際上是海底撈針I(yè)t is about getting the samples out, 我們需要取出樣品processing them, screening them 進行加工 篩選and hoping we find that that chemical compound 希望能發(fā)現(xiàn)一種化合物that is active against those disease areas. 能夠對某種疾病有效2

11、48第4集:藥物合成A known disease molecule, called the target, 一種已知的疾病分子 我們稱為靶分子is introduced to each of the two million compounds, one by one, 逐一加入到這兩百萬化合物中to see if anything happens. 去觀察是否有反應With the two million or so compounds, 在這兩百萬的化合物中we might get a few 我們可能會發(fā)現(xiàn)compounds that are active against that ta

12、rget. 一些化合物對靶分子有效We then have to take that one or two hits 然后我們得抓住這一個或兩個的機會and the chemists will make hundreds, maybe thousands, of samples 化學家根據(jù)它們的母核結構related to that original 合成出成千上萬的類似物structure to try and improve the activity 以期提高其活性and most importantly try 最重要的是to negate any safety or undesirab

13、le effects. 消除一切危險的和預期外的功效We have to screen those over and over 我們必須一遍一遍地篩選again to make sure that we're going in the right direction. 確保我們的方向正確After hundreds of millions of tests, 在數(shù)以萬計的測試后just a handful will make it through to trials on people. 只有少量的藥品會進行人體測試In all, it takes about 1 billion an

14、d 15 years' work 總的來說 需要10億的投入和15年的工作to find the winning compound that can become a licensed drug. 才能找到一種可以獲批投產(chǎn)的化合物The journey to a medicine is an epic journey. 尋找藥物的旅程是宏大的That whole process from idea through to a drug approved 從想法的形成到藥品審批通過的整個過程is one littered with failure. 失敗一直如影隨形249第5集:使人注意力

15、集中的藥His newfound ability to concentrate 他現(xiàn)在能夠集中注意力is largely thanks to a drug called methylphenidate, 多虧了這種叫哌醋甲酯的藥best known to most of us by a brand name - Ritalin. 大家更熟悉的是它的商品名 利他林It takes about 30-40 minutes for it to work, 大概30到40分鐘就能發(fā)揮藥效and it's not like Liam suddenly goes docile. 當然也并非利亞姆突

16、然就變溫順I(yè)t just basically does have a calming effect on him. 它只是有種鎮(zhèn)定的功效He doesn't seem to be as hyperactive 他不再過度亢奮on the medication and he is able to sit quietly, 服藥期間他可以安靜地坐著be able to focus on things like his homework 可以集中精力在他的作業(yè)上or just, just basically have 或者 只是.a more normal life, really. 只是過

17、上正常一點的生活And, as for thousands of other children, 如同對成千上萬其他孩子一樣Ritalin has had a remarkable effect on Liam. 利他林對利亞姆非常有效I feel calm. 我感覺很鎮(zhèn)靜I don't feel like excited. 沒有覺得很激動I feel energy because I 我以前覺得精力充沛can just run around all day if I wanted to 如果我愿意我可以跑一天but I'm just calm now. 但我現(xiàn)在只是覺得很鎮(zhèn)靜

18、And I'm excited as well. 也有點興奮250第6集:從藥物中獲利Liam, there's cars coming. Straight here now! 利亞姆 有車來了 趕緊過來And this is Ed. 這位是埃德I've just finished my law exams for this year. 我剛考完了今年的法律考試I've got a triathlon coming up in two days' time 我這兩天還得參加鐵人三項and I've got a couple of jobs 而且我

19、還有一堆工作on the go at the minute so things can be quite hectic. 最近忙個不停 所以事情很忙亂It does sometimes feel like 有時候我感覺there aren't quite enough hours in the day. 一天的時間并不夠用Don't, Liam! 不要 利亞姆!For very different reasons, 雖然原因不同both Ed and Liam have found benefits from the same drug. 埃德和利亞姆都從同種藥物中獲益Aged

20、 five, Liam was diagnosed 五歲的時候 利亞姆被確診為with attention deficit hyperactivity disorder, ADHD. 注意力不足過動癥 簡稱ADHDCome on, your hot chocolate's ready. 來吧 你的熱巧克力好了Now, five years later, 現(xiàn)在 五年過去了 Liam's life has been transformed. 利亞姆的生活有了很大改變Here you go. 到你了Thank you. One, two, three, four, five. Exc

21、use me. 謝謝 一二三四五 打斷一下Whose go is it next? 下一個到誰Mine? No it was me, you. 我 不是我 是你251第7集:治療各種疾病的藥物Despite the minute success rate, 盡管成功幾率微乎其微the potential rewards are enormous. 但潛在的回報卻是巨大的We hope there would be chemicals in here 我們希望這其中 有一種化學成分that would be the future cures for all sorts of disease ar

22、eas. 可以在未來治愈所有疾病It would be nice to think that here 想象一下就在這里we do have the cures for cancer, AIDS, Malaria, 能找到種藥物 治愈癌癥 艾滋病 瘧疾any of the world Health Organisation top priorities. 及所有世衛(wèi)組織高度關注的疾病 那該多好If drugs are not designed but discovered, 倘若藥物并非設計 而是偶然發(fā)現(xiàn)得來then it should come as no surprise that 那么

23、只有我們親身嘗試后we only find out what they really do to us when we take them. 才知道它真正的效用也并不奇怪Give me your hand. Give me your hand. Liam! 把手給我 把手給我 利亞姆This is Liam. 這是利亞姆Aged five, he was disruptive, hyperactive and unable to focus. 五歲 過度活躍 沒辦法集中252第8集:藥物的副作用Now without the medication, 如果沒有藥物幫助you could grou

24、nd Liam and he would go back the next day 你可以給利亞姆禁足 但第二天and do the same thing that he'd been grounded for. 他會又會重犯讓他禁足的錯誤With medication it just enables him to consider the consequences, 在藥物的幫助下 他可以去更清楚地a little bit more clearly, of his actions. 考慮行動的后果It was only by accident 研究人員是在偶然間that resear

25、chers discovered drugs like Ritalin 發(fā)現(xiàn)像利他林這種藥could help children with behavioural problems concentrate better. 可以幫助有行為問題的兒童更好地集中精力These drugs were originally designed 這些藥在50年前50 years ago for the treatment of adults with depression. 是為治療成人的抑郁癥而設計的It's only now 然而直到現(xiàn)在we are beginning to understan

26、d how they work. 我們才開始了解它的作用機理ADHD is believed to be caused by an imbalance ADHD是由于大腦中of key chemical messengers in the areas 控制注意力和工作記憶區(qū)域里的of the brain that control attention and working memory. 關鍵化學遞質不平衡引起的Ritalin appears to make these 利他林似乎能讓這些messengers more effective, helping to restore attenti

27、on. 遞質更加強效 進而幫助恢復注意力Like all drugs, Ritalin comes with a cost. 和所有藥物一樣 利他林也有副作用It can cause a loss of appetite and insomnia. 它可能引起食欲降低和失眠But now another benefit has 但現(xiàn)在又發(fā)現(xiàn)了它的另一個功效been revealed from which we could all profit. 可以惠及我們所有人253第9集:增強劑Initially when I took the Ritalin, I didn't feel any

28、 difference. 起初我吃它 并沒有感覺到不同Only really afterwards did I actually 等到一段時間過后notice that I felt slightly more focused than I usually do. 才發(fā)現(xiàn)我比平時更集中精力I found it really difficult to kind of get into that mental state 我發(fā)現(xiàn)要進入那種where I kind of felt I could just sit and do nothing. 干坐著不干活的精神狀態(tài)很困難I found mysel

29、f looking for things to occupy my attention. 我發(fā)現(xiàn)自己在找東西來占據(jù)注意力Ritalin can work as a cognitive enhancer. 利他林也可以用作認知增強劑 If a person without ADHD takes it, 如果一個沒有患ADHD的人服用它 it can make them cleverer. 它可以使他們更聰明It's a discovery not lost on the country's academic elite. 這個發(fā)現(xiàn)并沒有被學術精英們忽視Here at Cambri

30、dge University, students are abusing Ritalin 在劍橋大學 學生們?yōu)E用利他林or its close relative, modafinil, to help them get ahead. 或者它的類似物莫達非尼 來增進學業(yè)A few of my friends do what they call modafi-vising. 我的一些朋友服用他們所謂的莫達聰明劑It can keep them up for 24 hours and they can keep on going. 它可以使他們24小時保持興奮I think they feel pr

31、etty shocking after it, 我想他們過后肯定會很心煩意亂but if you need to do a lot of work in a short amount of time, 但如果要在短時間里完成大量工作then that's one way I've heard it can be done. 這就是我所知道的有效方法254第10集:藥物的好處People who do take Ritalin, I think they see 我認為服用利他林的人the benefits of it and it does help them with the

32、ir revision. 看到了它的好處 它的確幫助他們復習My friends that do, tend to do pretty well but I, 我的那些服用過的朋友表現(xiàn)更出色一些I like to think that's because they're quite clever. 但我還是愿意相信是因為他們天資聰穎Ed wasn't taking Ritalin for illicit gain. 埃德服用利他林 并非出于不當目的He took it at the behest of this woman. 他是在這位女士的委托下服用的Barbara

33、Sahakian is Professor of 芭芭拉·薩哈金Clinical Neuropsychology at Cambridge University. 是劍橋大學臨床神經(jīng)心理學的教授She's researching what drugs for 她在研究治療ADHD的藥物those with ADHD can do to the brains of the healthy. 對健康人大腦的作用Well, we knew that the drug worked as a cognitive enhancer 我們知道這個藥可以用作for conditions l

34、ike attention deficit hyperactivity disorder, 多動癥兒童的認知增強劑 but would they also work in, 但對沒有問題的健康人in healthy people who didn't have any problems? 它也能有作用嗎Could we actually boost cognition 我們真的可以in somebody who was you know functioning well? 提高健康人的認知能力嗎Ed was one of her research volunteers. 埃德是自愿受試

35、者之一They were each given Ritalin 他們每個人都服用利他林and put through a variety of intelligence tests. 并進行一系列的智力測試255 道德爭強論、Professor Sahakian found the drug had 薩哈金教授發(fā)現(xiàn)這種藥物also boosted levels of chemical messengers in healthy brains, 也可以提高健康大腦內(nèi)化學遞質的水平increasing their concentration levels too. 進而也提高他們的專注性We we

36、re a bit surprised that 我們有一些驚訝于in healthy people you could boost cognition. 它也可以提高健康人的認知能力It reveals ADHD is not a black and white disorder. 這表明 注意力不集中癥狀并不絕對It's a spectrum, a spectrum we are all on. 它只是個范圍 人人都可能有點Some people are very impulsive, 有些人很沖動other people are not impulsive at all. 有些人卻

37、一點也不I think we all know friends of 我想我們都認識這樣一些朋友ours who might do something that we wouldn't do 他們會做出我們不會做的事情and then it's a question of if we go 只要我們將范圍擴大further up that spectrum, that we may start to find somebody 我們就會開始發(fā)現(xiàn)who is actually not functioning very well 有些人并不是很健康because their imp

38、ulsive behaviour or their lack of attention 因為他們的行為沖動或缺乏注意力is very bad and therefore they do actually need a treatment. 是不好的表現(xiàn) 他們亟需治療This potential to make us all cleverer 這種使人變聰明的潛在可能性opens an ethical minefield. 引發(fā)一場道德上的爭論 256 藥物濫用If you want to do well, 如果你想要表現(xiàn)好I feel that should be a personal ach

39、ievement 我認為就應該靠個人努力as opposed to enhanced by artificial mechanisms. 而不是通過來人為的機制來提高If a lot of people took it, 如果大量的人服用它then people would have to 那么人們就必須服用take it to be able to compete with their peers. 這樣才能和同齡人競爭To be perfectly honest, doing what it does, if it was legal, 坦誠地說 如果這么做是合法的and it was s

40、afe, everyone would be doing it. 并且安全的 那么每個人都會服用Already it's being put to use among professionals. 現(xiàn)在一些專業(yè)人士已經(jīng)開始服用了Professors are using it to help them work, 教授們用它們來幫助工作and surgeons are looking at it 外科醫(yī)生們服用它as a way of staying alert during long and complex surgery. 是為了在長時間復雜手術中保持敏銳But for Profes

41、sor Sahakian 但是對于薩哈金教授the question remains 依然存在一個問題 will it actually make our lives better? 它真的能改善我們的生活嗎Suppose we took cognitive enhancing drugs 假如我們服用提高認知的藥物and we got all our work done in a short period of time, 我們在短時間內(nèi)把工作做完we could go home, spend time with our 我們就可以回家 和家人在一起family and improve ou

42、r work/life balance. That would be great. 改善工作與家庭之間的平衡 那很不錯But it's more likely with the 但是 當今社會type of society that we seem to be moving towards 正朝向無休止地工作發(fā)展that it will be this 24/7 因此更有可能出現(xiàn)的情況是society so we'll take these drugs so we can 我們服用這些藥物work longer, so we can travel more and do 是為了

43、讓做工作時間更長 旅行更多more work so it will 然后做更多的工作disrupt our work/life balance even more. 因此會使工作與生活的平衡變得更糟第13集:257暢銷藥物I'm always looking for ways that I can squeeze more in. 我一直都在想辦法擠出更多的時間At one point I did think I'm going 有時候 我真的認為to have to give up eating, sleeping or one of my jobs. 我會廢寢忘食 或是放棄

44、一項工作It did cross my mind actually that 我的確有過這樣的想法if I could get my hands on something like that again, 如果我能再一次服用那種藥物it would be, you know. maybe to my advantage. 也許 也許會增加我的優(yōu)勢I'm not sure about a pill 我不會用這種藥that would make you more intelligent. 這種能讓人變聰明的藥物We're happy being a bit. on the thic

45、k side. 我們就這樣笨笨的也挺開心的Yeah, being a bit thick's OK. 是的 笨一點也挺好的We'd like to think our drugs are designed 我們都一廂情愿地認為for exact purposes, 藥物是為特定目的而設計的but they're not as targeted as we think. 但是它們并不像我們想象的那么有準頭We only discover where in our bodies 當我們服藥的時候they work when we take them. 我們僅僅知道它的作用部

46、位It turns out Ventolin inhalers, 實際上 喘樂寧氣霧劑 a treatment for asthma, 一種治療哮喘的藥物can also prevent premature labour, 同樣可以預防早產(chǎn)and arsenic, a notorious poison, 砒霜 一種毒藥is making a comeback as a treatment for leukaemia. 正在白血病治療中嶄露頭角Even the fastest-selling drug 即便有史以來最暢銷的藥物of all time is not used for what it

47、 was designed. 它現(xiàn)在的用途也并非當初設計的初衷藥物依賴第12集:濫用藥物If you want to do well, 如果你想要表現(xiàn)好I feel that should be a personal achievement 我認為就應該靠個人努力as opposed to enhanced by artificial mechanisms. 而不是通過來人為的機制來提高If a lot of people took it, 如果大量的人服用它then people would have to 那么人們就必須服用take it to be able to compete wit

48、h their peers. 這樣才能和同齡人競爭To be perfectly honest, doing what it does, if it was legal, 坦誠地說 如果這么做是合法的and it was safe, everyone would be doing it. 并且安全的 那么每個人都會服用Already it's being put to use among professionals. 現(xiàn)在一些專業(yè)人士已經(jīng)開始服用了Professors are using it to help them work, 教授們用它們來幫助工作and surgeons are

49、 looking at it 外科醫(yī)生們服用它as a way of staying alert during long and complex surgery. 是為了在長時間復雜手術中保持敏銳But for Professor Sahakian 但是對于薩哈金教授the question remains 依然存在一個問題 will it actually make our lives better? 它真的能改善我們的生活嗎Suppose we took cognitive enhancing drugs 假如我們服用提高認知的藥物and we got all our work done

50、in a short period of time, 我們在短時間內(nèi)把工作做完we could go home, spend time with our 我們就可以回家 和家人在一起family and improve our work/life balance. That would be great. 改善工作與家庭之間的平衡 那很不錯But it's more likely with the 但是 當今社會type of society that we seem to be moving towards 正朝向無休止地工作發(fā)展that it will be this 24/7 因

51、此更有可能出現(xiàn)的情況是society so we'll take these drugs so we can 我們服用這些藥物work longer, so we can travel more and do 是為了讓做工作時間更長 旅行更多more work so it will 然后做更多的工作disrupt our work/life balance even more. 因此會使工作與生活的平衡變得更糟258第14集:治療心絞痛的藥It started life as UK 92480, 這個編號為UK92480的化合物one of millions of compounds

52、來自輝瑞制藥公司的新藥倉庫in the stores at the drug company Pfizer. 是千百萬個化合物中的一員They were looking for a new drug for angina, 當時專家們正在尋找治療心絞痛的新something that would relax blood vessels 一種能夠放松心臟around the heart. 周圍血管的藥物After screening hundreds of 在篩查過無數(shù)的化合物之后thousands of compounds, they ended up with UK 92480. 他們最終鎖

53、定了UK92480But its trials in humans were a let-down. 人體實驗結果卻不盡如人意It was about to be consigned 正當藥物要被重新收回倉庫時back to the stores when the trial volunteers 受試者們開始不斷索要藥片started coming back and reporting an unusual side-effect - 并反饋一種不同尋常的副作用lots of erections. 陰莖勃起Add the drug the relaxation's 加入藥物之后 其松

54、弛度變大get larger but its trace is upside down. 不過藥物作用曲線卻是反過來的By making a crude mock-up of the 通過制作人類性器官的粗略模擬模型human sexual apparatus, senior scientist Chris Wayman 高級研究員克里斯·韋曼使用了found an ingenious way to test this anecdotal evidence. 一種巧妙的方法來檢驗這種有趣的現(xiàn)象259第15集:藥物組合的神奇療效These are actually penile 組織浴

55、槽中放置的blood vessels that we have in a tissue bath. 是真的陰莖血管組織Think of this as the brain. 把這個看作是大腦This is the brain and the spinal cord. 這是大腦和脊髓When you're becoming aroused, 當你性喚起時 your brain switches on. 大腦就會激活We can mimic this by switching on 我們可以通過打開這些等同于the equivalent of the central nervous sys

56、tem in the brain. 中樞神經(jīng)系統(tǒng)的開關來模擬這一過程It sends electricity down 它將電流傳遞到to the tissue bath and across the tissues, 組織浴槽中 穿過組織and when we pass an electric current across these 當電流通過小片的陰莖組織時small pieces of penile tissue, they relax and 它們就會松弛下來ultimately that's what happens during penile erection. 事實上

57、這就是陰莖勃起的過程Relaxed penile blood vessels mean 陰莖血管松弛more blood flow to the penis, and so an erection. 意味著更過血液流向陰莖 導致勃起What Chris did was take penile blood vessels 克里斯從陽痿病人體內(nèi)from impotent men, 提取了陰莖血管組織vessels that didn't respond 當大腦開關被打開的時候 when he flicked the brain switch, 血管組織并沒有產(chǎn)生反應and then added UK 92480 to the tissue bath. 隨后將UK92480加入組織浴槽中What was most amazing about this study 最不可思議的事情發(fā)生了was that we saw a restoration of erectile response. 陰莖組織重新出現(xiàn)了勃起反應It's very rare in any tissue preparation 在任何組織標本里 由功能障礙to convert dysfunctional to normal function, and so now 到功能正常的轉變都是很罕見的we w