TED英语演讲：长生不老的细胞科学
Where does the end begin?Well, for me, it all began with this little fellow.This adorable organism --well, I think it’s adorable --is called Tetrahymena and it’s a single-celled creature.It’s also been known as pond scum.So that’s right, my career started with pond scum.
结束是从何开始的?对我来说，它开始于这个小家伙。这可爱的有机体，我认为它很可爱，它叫做四膜虫，是种单细胞生物。它也就是池塘浮渣。是的，我的职涯始于池塘浮渣。
Now, it was no surprise I became a scientist.Growing up far away from here,as a little girl I was deadly curiousabout everything alive.I used to pick up lethally poisonous stinging jellyfish and sing to them.And so starting my career,I was deadly curious about fundamental mysteriesof the most basic building blocks of life,and I was fortunate to live in a society where that curiosity was valued.
我变成科学家并不让人意外。我在离这里很远的地方长大，我小时候非常有好奇心，对所有的生物都好奇。我以前会捡起有致命剧毒会螫人的水母，然后对牠们唱歌。所以，开始我的职涯时，我非常好奇，想解开很根本的谜题，想知道构成生命的基础积木是什么，很幸运，我所在的社会很重视好奇心。
Now, for me, this little pond scum critter Tetrahymenawas a great way to study the fundamental mysteryI was most curious about:those bundles of DNA in our cells called chromosomes.And it was because I was curious about the very ends of chromosomes,known as telomeres.Now, when I started my quest,all we knew was that they helped protect the ends of chromosomes.It was important when cells divide.It was really important,but I wanted to find out what telomeres consisted of,and for that, I needed a lot of them.And it so happens that cute little Tetrahymenahas a lot of short linear chromosomes,around 20,000,so lots of telomeres.And I discovered that telomeres consisted of special segmentsof noncoding DNA right at the very ends of chromosomes.
对我而言，四膜虫这池塘浮渣小生物是研究我很好奇的根本谜题的好方式：我们的细胞内大量的 DNA，也就是所谓的染色体。因为我对染色体的末端很好奇，也就是所谓的端粒。当我开始探索，我们只知道：它们协助保护染色体的末端。细胞分裂时，这点很重要。它相当重要，但我想要了解端粒是什么组成的，为这个目的，我需要很多端粒。刚好这个可爱的小四膜虫有很多短短线性的染色体。大约两万个，所以会有很多端粒。我发现端粒包括位在染色体很末端未编码的特殊 DNA 区段。
But here’s a problem.Now, we all start life as a single cell.It multiples to two.Two becomes four. Four becomes eight,and on and on to form the 200 million billion cellsthat make up our adult body.And some of those cells have to divide thousands of times.In fact, even as I stand here before you,all throughout my body, cells are furiously replenishingto, well, keep me standing here before you.So every time a cell divides, all of its DNA has to be copied,all of the coding DNA inside of those chromosomes,because that carries the vital operating instructionsthat keep our cells in good working order,so my heart cells can keep a steady beat,which I assure you they’re not doing right now,and my immune cellscan fight off bacteria and viruses,and our brain cells can save the memory of our first kissand keep on learning throughout life.
但，有一个问题。生命是从单细胞开始的。一个会变成两个，两个变成四个，四个变成八个，一路这样下去，形成了二十万兆个细胞，组成了成人的身体。有些细胞需要分裂数千次。事实上，即使我站在各位面前，我整个身体的细胞正疯狂地补充，让我能够持续站在你们面前。每当一个细胞分裂，它所有的 DNA 都会被复制，那些染色体中所有编码的 DNA，因为那带有极重要的运作指示，让我们的细胞能处于良好的工作状态，这么一来我的心脏细胞才能保持稳定的心跳，我向各位保证，它们现在并没做到，而我的免疫细胞，能击退细菌和病毒，我们的头脑细胞能储存我们初吻的记忆，并在整个人生中持续学习。
But there is a glitch in the way DNA is copied.It is just one of those facts of life.Every time the cell divides and the DNA is copied,some of that DNA from the ends gets worn down and shortened,some of that telomere DNA.And think about itlike the protective caps at the ends of your shoelace.And those keep the shoelace, or the chromosome, from fraying,and when that tip gets too short, it falls off,and that worn down telomere sends a signal to the cells.The DNA is no longer being protected.It sends a signal. Time to die.So, end of story.
但复制 DNA 的方式有个小毛病，仅是生命的事实之一。每当细胞分裂、DNA 被复制，某些末端 DNA 会磨损缩短，一些端粒的 DNA。可以用这方式来想：就像你的鞋带末端的保护套。它们能让鞋带或染色体不会被磨损，当尖端变得太短时，它就会脱落，而那被磨损掉的端粒就会发送一个讯号给细胞。「这 DNA 不再受到保护。」它发出讯号。是死亡的时候了。所以，故事结束。
Well, sorry, not so fast.It can’t be the end of the story,because life hasn’t died off the face of the earth.So I was curious:if such wear and tear is inevitable,how on earth does Mother Nature make surewe can keep our chromosomes intact?
抱歉，没那么快。故事不可能这样结束，因为生命还没从地球表面上消逝。所以我很好奇：如果这种损耗是无可避免的，大自然到底要如何确保我们能保持不让染色体受损?
Now, remember that little pond scum critter Tetrahymena?The craziest thing was,Tetrahymena cells never got old and died.Their telomeres weren’t shortening as time marched on.Sometimes they even got longer.Something else was at work,and believe me, that something was not in any textbook.So working in my lab with my extraordinary student Carol Greider --and Carol and I shared the Nobel Prize for this work --we began running experimentsand we discovered cells do have something else.It was a previously undreamed-of enzymethat could replenish,make longer, telomeres,and we named it telomerase.And when we removed our pond scum’s telomerase,their telomeres ran down and they died.So it was thanks to their plentiful telomerasethat our pond scum critters never got old.
还记得那池塘浮渣小生物四膜虫吗?很疯狂的是，四膜虫细胞从来不会变老或死亡。牠们的端粒并不会随时间而变短。有时甚至还会变长。还有某样东西在运作，相信我，那某样东西并不在任何教科书中。所以，我和杰出学生凯洛葛莱德在实验室中合作──凯洛和我共享这项研究赢得的诺贝尔奖──我们开始进行实验，我们发现细胞的确有其他的东西。是先前意想不到的酶(酵素)，它能补充端粒，让端粒更长，我们将它命名为「端粒酶」。当我们移除池塘浮渣的端粒酶后，牠们的端粒就会耗尽而死亡。所以要归功于丰富的端粒酶，我们的池塘浮渣才能永生不老。
OK, now, that’s an incredibly hopeful messagefor us humans to be receiving from pond scum,because it turns outthat as we humans age, our telomeres do shorten,and remarkably,that shortening is aging us.Generally speaking,the longer your telomeres,the better off you are.It’s the overshortening of telomeresthat leads us to feel and see signs of aging.My skin cells start to dieand I start to see fine lines, wrinkles.Hair pigment cells die.You start to see gray.Immune system cells die.You increase your risks of getting sick.In fact, the cumulative research from the last 20 yearshas made clear that telomere attritionis contributing to our risks of getting cardiovascular diseases,Alzheimer’s, some cancers and diabetes,the very conditions many of us die of.
那是我们人类能从池塘浮渣身上得到的一个非常有希望的讯息，因为结果发现，随着我们人类年纪增长，我们的端粒确实会变短，很惊人的是，那缩短现象让我们变老。一般来说，你的端粒越长，你的状况就会越好。是端粒过度减短的现象导致我们会感到及看到老化的征象。我的皮肤细胞开始死亡，我就会开始看到线条、皱纹。头发色素细胞死亡，你就会开始看到白发。免疫细胞死亡，你被攻击的风险就会提升。事实上，过去二十年所累积的研究清楚地指出，端粒损耗可能造成罹患像是：心血管疾病、阿滋海默症、某些癌症，以及糖尿病等许多致死疾病的风险。
And so we have to think about this.What is going on?This attrition,we look and we feel older, yeah.Our telomeres are losing the war of attrition faster.And those of us who feel youthful longer,it turns out our telomeres are staying longerfor longer periods of time,extending our feelings of youthfulnessand reducing the risks of all we most dreadas the birthdays go by.
所以我们得要想想这一点。发生了什么事?这种损耗，我们看起来且感觉起来变老了。我们的端粒在损耗之战中败退得很快。至于觉得年轻时间比较长的人，结果发现是端粒能留比较久，比较长的时间，延长我们对于年轻的感觉，并减少我们随着每个生日过去而很害怕的那些风险。
OK,seems like a no-brainer.Now, if my telomeres are connectedto how quickly I’m going to feel and get old,if my telomeres can be renewed by my telomerase,then all I have to do to reverse the signs and symptoms of agingis figure out where to buy that Costco-sized bottleof grade A organic fair trade telomerase, right?Great! Problem solved.
好。似乎很简单。如果我的端粒和我多快感到变老及实际变老是有关联的，如果我能用端粒酶来复原端粒，那么若我想要反转老化的征兆和症状，就是要找个地方买像好市多那样超大罐、A 级、有机、公平贸易的端粒酶，对吧?好极了!问题解决。
(Applause)
(掌声)
Not so fast, I’m sorry.Alas, that’s not the case.OK. And why?It’s because human genetics has taught usthat when it comes to our telomerase,we humans live on a knife edge.OK, simply put,yes, nudging up telomerase does decrease the risks of some diseases,but it also increases the risks of certain and rather nasty cancers.So even if you could buy that Costco-sized bottle of telomerase,and there are many websites marketing such dubious products,the problem is you could nudge up your risks of cancers.And we don’t want that.
很抱歉，没那么快。唉，并不是那样的。那为什么呢?因为人类遗传学教导我们，谈到我们的端粒酶时，我们人类是住在刀缘上的。简单来说，是的，增加端粒酶的确可以减少一些疾病的风险，但同时也会增加某些很糟糕的癌症的风险。所以，就算你能买到像好市多那样超大罐的端粒酶，有许多网站在行销这类可疑的产品，问题是你有可能增加罹癌的风险。我们不想要那样。
Now, don’t worry,and because, while I think it’s kind of funny that right now,you know, many of us may be thinking,well, I’d rather be like pond scum.
别担心，因为，虽然我觉得有点好笑，也许此刻很多人正想着，我宁可像池塘浮渣一样。
(Laughter)
(笑声)
There is something for us humansin the story of telomeres and their maintenance.But I want to get one thing clear.It isn’t about enormously extending human lifespanor immortality.It’s about health span.Now, health span is the number of years of your lifewhen you’re free of disease,you’re healthy, you’re productive,you’re zestfully enjoying life.Disease span, the opposite of health span,is the time of your life spent feeling old and sick and dying.So the real question becomes,OK, if I can’t guzzle telomerase,do I have control over my telomeres’ lengthand hence my well-being, my health,without those downsides of cancer risks?OK?
在这关于端粒以及维护端粒的真相中还是有我们人类可以学习之处。但我想先澄清一件事。重点并不是将人类寿命期间延长很多或是永生不死。重点是「健康期间」。健康期间，就是你人生中有多少年是没有疾病、很健康、有生产力、能够热情享受人生的。相对于健康期间的「疾病期间」，指的就是你人生中有多长时间觉得自己老、病、和垂死。所以，真正的问题变成是，如果我无法狂饮端粒酶，我是否能控制端粒酶的长度，进而控制我的福祉、我的健康，而没有癌症风险的坏处?好吗?
So, it’s the year 20xx.Now, I’ve been minutely scrutinizing little teeny tiny telomeresvery happily for many years,when into my lab walks a psychologist named Elissa Epel.Now, Elissa’s expertise is in the effects of severe, chronic psychological stresson our mind’s and our body’s health.And there she was standing in my lab,which ironically overlooked the entrance to a mortuary, and --
所以，那是 20xx 年。多年来，我很快乐地、分分钟钟地持续仔细观察著那些极微小的端粒，直到有一天，名叫伊莉莎埃佩尔的心理学家走入了我的实验室。伊莉莎的专长在于严重慢性心理压力对于我们身、心健康的影响。她出现在我的实验室，很讽刺的是从实验室可以眺望停尸间的入口，而且──
(Laughter)
(笑声)
And she had a life-and-death question for me.What happens to telomeres in people who are chronically stressed?she asked me.You see, she’d been studying caregivers,and specifically mothers of children with a chronic condition,be it gut disorder,be it autism, you name it --a group obviously under enormous and prolonged psychological stress.I have to say, her questionchanged me profoundly.See, all this time I had been thinking of telomeresas those miniscule molecular structures that they are,and the genes that control telomeres.And when Elissa asked me about studying caregivers,I suddenly saw telomeres in a whole new light.I saw beyond the genes and the chromosomesinto the lives of the real people we were studying.And I’m a mom myself,and at that moment,I was struck by the image of these womendealing with a child with a conditionvery difficult to deal with,often without help.And such women, simply,often look worn down.So was it possible their telomeres were worn down as well?
她有个生死问题要问我。「有慢性压力的人，他们的端粒会发生什么事?」她这样问我。她一直在研究照护者，特别慢性病孩童的母亲，可能是肠病，可能是自闭症，任何你想得到的──这个族群很显然处在巨大且长期的心理压力之下。我不得不说，她的问题深深改变了我。一直以来，我从小分子结构的角度来思考端粒和控制端粒的基因。当伊莉莎问我关于照护者的问题时，我突然从全新的角度去看端粒。我超越了基因和染色体，看到我们所研究的真实人类的生活。我自己也是个母亲，在那一刻，我被这个影像震撼了：这些女子通常靠一己之力照顾孩子，有非常难处理的疾病的孩子，往往没有帮手。这类女子，很显而易见，经常看起来是耗尽了精力的模样。有没有可能她们的端粒也被损耗掉了呢?
So our collective curiosity went into overdrive.Elissa selected for our first study a group of such caregiving mothers,and we wanted to ask:What’s the length of their telomerescompared with the number of years that they have been caregivingfor their child with a chronic condition?So four years go byand the day comes when all the results are in,and Elissa looked down at our first scatterplotand literally gasped,because there was a pattern to the data,and it was the exact gradient that we most feared might exist.It was right there on the page.The longer, the more years that is,the mother had been in this caregiving situation,no matter her age,the shorter were her telomeres.And the more she perceivedher situation as being more stressful,the lower was her telomerase and the shorter were her telomeres.
我们共同的好奇心促使我们加倍努力。伊莉莎为我们的*一项研究选了一群照护母亲，我们想要问：她们的端粒长度和她们照顾有慢性疾病孩童多少年有什么关联?所以，经过了四年，所有结果都进来的那一天，伊莉莎看着我们的*一张资料散布图，真的是倒抽了一口气，因为资料的确呈现出了模式，且正是我们很怕存在的斜线。就在那里，呈现在那一页上。母亲在照护情境中的时间越久、越多年，不论她几岁，她的端粒都会比较短。而且，她若越是感受到她所处的情境有很大的压力，她的端粒酶就会越少，她的端粒也就会越短。
So we had discovered something unheard of:the more chronic stress you are under,the shorter your telomeres,meaning the more likely you were to fall victim to an early disease spanand perhaps untimely death.Our findings meant that people’s life eventsand the way we respond to these eventscan change how you maintain your telomeres.So telomere length wasn’t just a matter of age counted in years.Elissa’s question to me,back when she first came to my lab, indeed had been a life-and-death question.
所以我们发现了以前没听过的事：越是在长期压力之下，你的端粒就会越短，意味着，你越可能很早就罹患疾病，也可能很终会比较早死。我们的发现意味着，人一生经历的事件、以及我们对这些事件的因应方式，能够改变你的端粒的维护状况。所以端粒长度并不只是把年龄换算成年数。伊莉莎一开始到我实验室问的问题，的确是个生死的问题。
Now, luckily, hidden in that data there was hope.We noticed that some mothers,despite having been carefully caring for their children for many years,had been able to maintain their telomeres.So studying these women closely revealed that they were resilient to stress.Somehow they were able to experience their circumstancesnot as a threat day in and day outbut as a challenge,and this has led to a very important insight for all of us:we have control over the way we ageall the way down into our cells.
幸运的是，在那些资料中也藏有希望。我们注意到，有些母亲虽然多年来都一直很细心照顾她们的孩子，却仍然能维持着她们的端粒。仔细研究这些女性，发现她们对压力的恢复力很强。她们能够以某种方式，不一天到晚视她们所经历的情况为威胁，而视为是挑战，这就导出了对于我们所有人都非常重要的洞见：我们能够控制我们老化的方式且一路控制到我们的细胞。
OK, now our initial curiosity became infectious.Thousands of scientists from different fieldsadded their expertise to telomere research,and the findings have poured in.It’s up to over 10,000 scientific papers and counting.So several studies rapidly confirmed our initial findingthat yes, chronic stress is bad for telomeres.And now many are revealingthat we have more control over this particular aging processthan any of us could ever have imagined.A few examples:a study from the University of California, Los Angelesof people who are caring for a relative with dementia, long-term,and looked at their caregiver’s telomere maintenance capacityand found that it was improvedby them practicing a form of meditationfor as little as 12 minutes a day for two months.Attitude matters.If you’re habitually a negative thinker,you typically see a stressful situation with a threat stress response,meaning if your boss wants to see you,you automatically think, "I’m about to be fired,"and your blood vessels constrict,and your level of the stress hormone cortisol creeps up,and then it stays up,and over time, that persistently high level of the cortisolactually damps down your telomerase.Not good for your telomeres.
我们一开始的好奇心变成是有感染力的。数以千计来自不同领域的科学家把他们的专长加到了端粒的研究当中，大量的发现涌入。有超过一万份科学论文，且还在增加中。所以，有许多研究很快就确认了我们很初的发现，是的，长期压力对于端粒有害。现在，许多研究指出，我们对于这种老化的过程所能掌控的程度，远超过任何人过去的想像。举几个例子：洛杉矶加州大学的一篇研究，对象是关于长期照顾失忆亲戚的人，该研究探究了这些照护者的端粒维护能力，发现他们如果连续两个月每天进形某种形式的冥想，即使只有短短十二分钟，也能改善这项能力。态度很重要。如果你是个习惯性负面思考的人，你通常遇到有压力的情境时会产生威胁性的压力反应，意思是说，如果你的老板想见你，你自动会想：「我要被开除了。」你的血管会收缩，你的压力贺尔蒙皮质醇会升高，且一直维持很高，随着时间过去，一直持续很高的皮质醇其实就会减弱你的端粒酶。这对你的端粒不好。
On the other hand,if you typically see something stressful as a challenge to be tackled,then blood flows to your heart and to your brain,and you experience a brief but energizing spike of cortisol.And thanks to that habitual "bring it on" attitude,your telomeres do just fine.So ...What is all of this telling us?Your telomeres do just fine.You really do have power to change what is happeningto your own telomeres.
另一方面，如果你通常视很有压力的事情为要对付的挑战，那么，血液就会流向你的心脏和大脑，你就会经历到短暂但让人精力充沛的皮质醇增强。托那「放马过来吧」习惯的福，你的端粒就会好好的。所以，这一切告诉我们什么?你的端粒好好的。你真的有力量可以改变你自己的端粒会发生什么事。
But our curiosity just got more and more intense,because we started to wonder,what about factors outside our own skin?Could they impact our telomere maintenance as well?You know, we humans are intensely social beings.Was it even possible that our telomeres were social as well?And the results have been startling.As early as childhood,emotional neglect, exposure to violence,bullying and racismall impact your telomeres,and the effects are long-term.Can you imagine the impact on childrenof living years in a war zone?People who can’t trust their neighborsand who don’t feel safe in their neighborhoodsconsistently have shorter telomeres.So your home address matters for telomeres as well.On the flip side,tight-knit communities,being in a marriage long-term,and lifelong friendships, even,all improve telomere maintenance.
但我们的好奇心变得越来越强烈，因为我们开始纳闷，我们身外的因素如何呢?它们能否影响我们的端粒维护呢?要知道，我们人类是极为社交的动物。有没有可能我们的端粒也很社交呢?而结果十分惊人。早至孩童时期，情绪忽视、接触暴力、霸凌、及种族主义，都会影响你的端粒，且影响是长期的。你们能想像在战区内的孩子，寿命会受到什么样的影响?无法信任邻居的人，在邻坊中没有安全感的人，很一致地，都有比较短的端粒。所以你住哪里，对于端粒也很重要。反过来说，紧密连结的社区、长期的婚姻、甚至一生的友谊，都能改善端粒的维护。
So what is all this telling us?It’s telling us that I have the power to impact my own telomeres,and I also have the power to impact yours.Telomere science has told us just how interconnected we all are.
所以，这一切告诉我们什么?它告诉我们，我有力量可以影响我自己的端粒，我也有力量可以影响你的端粒。端粒科学告诉我们，我们是多么紧密连结在一起。
But I’m still curious.I do wonderwhat legacy all of uswill leave for the next generation?Will we investin the next young woman or manpeering through a microscope at the next little critter,the next bit of pond scum,curious about a question we don’t even know today is a question?It could be a great question that could impact all the world.And maybe, maybe you’re curious about you.Now that you know how to protect your telomeres,are you curious what are you going to dowith all those decades of brimming good health?And now that you know you could impact the telomeres of others,are you curioushow will you make a difference?And now that you know the power of curiosity to change the world,how will you make sure that the world invests in curiosityfor the sake of the generations that will come after us?
但我仍然好奇。我确实纳闷，我们所有人会留给下一代什么遗产?我们是否会投资给接下来的年轻男、女，透过显微镜盯着下一个小生物、下一坨池塘浮渣，对我们现今仍未知的问题感到好奇?那可能是个好问题，能够影响全世界。也许你对你自己很好奇。现在你知道如何保护你的端粒了，你是否会好奇，未来数十年你将会做些什么来维持好健康?现在你知道你能够影响他人的端粒了，你是否会好奇，你将会如何造成不同?现在你知道好奇的力量可以改变世界了，你要如何确保世界会为了我们之后的世代而投资在好奇心上?
Thank you.
谢谢。
(Applause)
(掌声)