听力课堂TED音频栏目主要包括TED演讲的音频MP3及中英双语文稿，供各位英语爱好者学习使用。本文主要内容为演讲MP3+双语文稿:我们可以用干细胞再生心肌吗？，希望你会喜欢！
【演讲人及介绍】Chuck Murry
查克·莫里，医生，科学家
【演讲主题】我们可以用干细胞再生心肌吗？
【演讲文稿-中英文】
Translated by Lipeng Chen Reviewed by HomerLi
00:00
I'd like to tell you about a patient namedDonna. In this photograph, Donna was in her mid-70s, a vigorous, healthy woman,the matriarch of a large clan. She had a family history of heart disease,however, and one day, she had the sudden onset of crushing chest pain. Nowunfortunately, rather than seeking medical attention, Donna took to her bed forabout 12 hours until the pain passed. The next time she went to see herphysician, he performed an electrocardiogram, and this showed that she'd had alarge heart attack, or a "myocardial infarction" in medical parlance.
我想和你们讲讲一个叫唐娜的病人。在这张照片中，唐娜70多岁，一个精力充沛、健康的女人，也是一个大家族的领袖。但她有心脏病家族史，有一天，她突然感到胸痛。不幸的是，唐娜没有寻求医疗救助，而是在床上躺了大约12个小时，直到疼痛过去。下次她去看医生时，医生做了心电图，这表明她心脏病发了，或者医学术语中的“心肌梗塞”。
00:33
After this heart attack, Donna was neverquite the same. Her energy levels progressively waned, she couldn't do a lot ofthe physical activities she'd previously enjoyed. It got to the point where shecouldn't keep up with her grandkids, and it was even too much work to go out tothe end of the driveway to pick up the mail. One day, her granddaughter came byto walk the dog, and she found her grandmother dead in the chair. Doctors saidit was a cardiac arrhythmia that was secondary to heart failure. But the lastthing that I should tell you is that Donna was not just an ordinary patient.Donna was my mother.
在这次心脏病发作之后，唐娜就再也不一样了。她的体能逐渐下降，她不能做很多以前喜欢的体育活动。逐渐到了她不能跟上孙子孙女的地步，而且要走到楼道尽头去拿邮件也变得费劲了。一天，她的孙女过来遛狗，她发现奶奶死在椅子上。医生说这是一种继发于心力衰竭的心律失常。但我最后要告诉你们的是，唐娜不仅仅是个普通病人。唐娜是我母亲。
01:09
Stories like ours are, unfortunately, fartoo common. Heart disease is the number one killer in the entire world. In theUnited States, it's the most common reason patients are admitted to thehospital, and it's our number one health care expense. We spend over a 100billion dollars -- billion with a "B" -- in this country every yearon the treatment of heart disease. Just for reference, that's more than twicethe annual budget of the state of Washington.
不幸的是，像我们这样的故事太普遍了。心脏病是全世界头号杀手。在美国，这是病人入院的最常见原因，这是我们最大的医疗费用。我们花了1000多亿美元——1000多亿美元——在这个国家每年用于心脏病的治疗。顺便说下，这是华盛顿州年度预算的两倍多。
01:33
What makes this disease so deadly? Well, itall starts with the fact that the heart is the least regenerative organ in thehuman body. Now, a heart attack happens when a blood clot forms in a coronaryartery that feeds blood to the wall of the heart. This plugs the blood flow,and the heart muscle is very metabolically active, and so it dies very quickly,within just a few hours of having its blood flow interrupted. Since the heartcan't grow back new muscle, it heals by scar formation. This leaves the patientwith a deficit in the amount of heart muscle that they have. And in too manypeople, their illness progresses to the point where the heart can no longerkeep up with the body's demand for blood flow. This imbalance between supplyand demand is the crux of heart failure.
是什么使这种疾病如此致命？这一切都是因为心脏是在人体内再生能力最小的器官。当将血液注入心脏壁的冠状动脉中形成血液凝块时，心脏病就会发作。这会堵塞血流，心脏肌肉的新陈代谢非常活跃，所以在血液流动中断后的几个小时内，心脏很快就死了。因为心脏不能长出新的心肌，它通过形成疤痕而愈合。这使病人在心肌数量上形成了短缺。在太多的人身上，他们的病情已经坏到心脏无法满足身体对血液流动的需求。供求失衡是心力衰竭的症结所在。
02:22
So when I talk to people about thisproblem, I often get a shrug and a statement to the effect of, "Well, youknow, Chuck, we've got to die of something."
所以当我和人们谈论这个问题时，我经常会耸耸肩，然后说一句话，“好吧，你知道，查克，我们总会为某件事而死。”
02:32
(Laughter)
（笑）
02:36
And yeah, but what this also tells me isthat we've resigned ourselves to this as the status quo because we have to. Ordo we? I think there's a better way, and this better way involves the use ofstem cells as medicines.
是的，但这也告诉了我，我们已经对这个现状自我放弃了。真是这样吗？我觉得有更好的方法，这种更好的方法包括使用干细胞作为药物。
02:54
So what, exactly, are stem cells? If youlook at them under the microscope, there's not much going on. They're justsimple little round cells. But that belies two remarkable attributes. The firstis they can divide like crazy. So I can take a single cell, and in a month'stime, I can grow this up to billions of cells. The second is they candifferentiate or become more specialized, so these simple little round cellscan turn into skin, can turn into brain, can turn into kidney and so forth.Now, some tissues in our bodies are chock-full of stem cells. Our bone marrow,for example, cranks out billions of blood cells every day. Other tissues likethe heart are quite stable, and as far as we can tell, the heart lacks stemcells entirely. So for the heart, we're going to have to bring stem cells infrom the outside, and for this, we turn to the most potent stem cell type, thepluripotent stem cell. Pluripotent stem cells are so named because they canturn into any of the 240-some cell types that make up the human body.
那么，究竟什么是干细胞？如果你在显微镜下观察它们，太简单了。它们只是简单的小圆形细胞。但这掩盖了两个显著的特征。首先，它们可以疯狂地分裂。所以我只需要一个细胞，一个月后，我可以把它长到数十亿个细胞。第二，它们可以分化或变得更具指向性，所以这些简单的圆形细胞可以变成皮肤，可以变成大脑，可以变成肾脏等等。现在，我们体内的一些组织充满了干细胞。例如，我们的骨髓每天产生数十亿个血细胞。心脏等其他组织相当稳定，据我们所知，心脏完全缺乏干细胞。所以对于心脏来说，我们必须从外部引进干细胞，为此，我们转向最有效的干细胞类型，多能干细胞。多能干细胞就是这样命名的，因为它们可以变成构成人体的 240种细胞类型中的?任何一种。
03:54
So this is my big idea: I want to take humanpluripotent stem cells, grow them up in large numbers, differentiate them intocardiac muscle cells and then take them out of the dish and transplant theminto the hearts of patients who have had heart attacks. I think this is goingto reseed the wall with new muscle tissue, and this will restore contractilefunction to the heart.
这是我的想法：我想培养人类多能干细胞，让它们大量分裂，进而分化为心肌细胞，然后把它们从培养皿中拿出来，再把它们移植到心脏病患者的心脏上。我认为新的心肌细胞会缝合心脏上的伤口，进而会恢复心脏的收缩功能。
04:17
(Applause)
（掌声，欢呼）?
04:24
Now, before you applaud too much, this wasmy idea 20 years ago.
在你们鼓太多掌之前，我想说这是我20年前的想法。
04:27
(Laughter)
（笑）
04:29
And I was young, I was full of it, and Ithought, five years in the lab, and we'll crank this out, and we'll have thisinto the clinic. Let me tell you what really happened.
我很年轻，我充满了这种想法，我想，在实验室里呆五年，我们会解决这个问题的，我们会把这个想法在临床上变成现实。我来告诉你们到底发生了什么。
04:40
(Laughter)
（笑）
04:41
We began with the quest to turn thesepluripotent stem cells into heart muscle. And our first experiments worked,sort of. We got these little clumps of beating human heart muscle in the dish,and that was cool, because it said, in principle, this should be able to bedone. But when we got around to doing the cell counts, we found that only oneout of 1,000 of our stem cells were actually turning into heart muscle. Therest was just a gemisch of brain and skin and cartilage and intestine. So howdo you coax a cell that can become anything into becoming just a heart musclecell?
我们开始探索将这些多能干细胞转化为心肌细胞。我们的第一个实验差不多算成功了。我们在培养皿中放了一些跳动的人体心脏肌肉，这很酷，因为它表明，原则上我的想法应该可以做到。但当我们开始做细胞计数时，我们发现1000个干细胞中只有一个实际上变成了心肌细胞。其余的只是大脑细胞、皮肤细胞、软骨细胞和肠道细胞的混合。那么你如何让一个能变成任何东西的细胞?只变成心肌细胞呢？
05:20
Well, for this we turned to the world ofembryology. For over a century, the embryologists had been pondering themysteries of heart development. And they had given us what was essentially aGoogle Map for how to go from a single fertilized egg all the way over to ahuman cardiovascular system. So we shamelessly absconded all of this informationand tried to make human cardiovascular development happen in a dish. It took usabout five years, but nowadays, we can get 90 percent of our stem cells to turninto cardiac muscle -- a 900-fold improvement. So this was quite exciting.
为了这个，我们转向胚胎学的世界。一个多世纪以来，胚胎学家一直在思考心脏发育的奥秘。他们给了我们一张类似谷歌地图的东西，这指示如何从一个受精卵一直发展到人类心血管系统。所以我们贪婪地使用了所有这些信息，并试图使人的心血管发育发生在一个培养皿里。我们花了五年时间，但现在，我们可以让90%的干细胞变成心肌细胞——提高了900倍。所以这很令人兴奋。
05:56
This slide shows you our current cellularproduct. We grow our heart muscle cells in little three-dimensional clumpscalled cardiac organoids. Each of them has 500 to 1,000 heart muscle cells init. If you look closely, you can see these little organoids are actuallytwitching; each one is beating independently. But they've got another trick uptheir sleeve. We took a gene from jellyfish that live in the Pacific Northwest,and we used a technique called genome editing to splice this gene into the stemcells. And this makes our heart muscle cells flash green every time they beat.
这张幻灯片向你们展示我们当前的细胞产物。我们的心肌细胞在被称为心脏类器官的三维结构中发育。它们每个都有500到 1000个心肌细胞。如果你仔细观察，你会发现这些小的类器官实际上在运动；每个类器官都在独立地跳动。但它们还有另一个小奥秘。我们从太平洋西北部的水母身上提取了一个基因，我们使用了一种叫做基因组编辑的技术把这个基因拼接到干细胞中。这使得我们的心肌细胞每跳动一次都会闪烁绿色。
06:29
OK, so now we were finally ready to beginanimal experiments. We took our cardiac muscle cells and we transplanted theminto the hearts of rats that had been given experimental heart attacks. A monthlater, I peered anxiously down through my microscope to see what we had grown,and I saw ... nothing. Everything had died. But we persevered on this, and wecame up with a biochemical cocktail that we called our "pro-survivalcocktail," and this was enough to allow our cells to survive through thestressful process of transplantation. And now when I looked through themicroscope, I could see this fresh, young, human heart muscle growing back inthe injured wall of this rat's heart. So this was getting quite exciting.
现在，我们终于准备好开始动物实验了。我们取了我们的心肌细胞，把它们移植到有实验性心脏病发作的老鼠的心脏里。一个月后，我焦急地透过显微镜观察，看看我们长出了什么，我看到…没有什么。一切都死了。但我们坚持不懈，想出了一种生化鸡尾酒，我们称之为“助生鸡尾酒”，这足以通过移植的压力，让我们的细胞存活下来。现在当我通过显微镜看的时候，我能看到这些新鲜的、年轻的人类心肌?在受伤的老鼠心脏壁上生长。这变得非常令人兴奋。
07:13
The next question was: Will this new musclebeat in synchrony with the rest of the heart? So to answer that, we returned tothe cells that had that jellyfish gene in them. We used these cells essentiallylike a space probe that we could launch into a foreign environment and thenhave that flashing report back to us about their biological activity. Whatyou're seeing here is a zoomed-in view, a black-and-white image of a guineapig's heart that was injured and then received three grafts of our humancardiac muscle. So you see those sort of diagonally running white lines. Eachof those is a needle track that contains a couple of million human cardiacmuscle cells in it. And when I start the video, you can see what we saw when welooked through the microscope. Our cells are flashing, and they're flashing insynchrony, back through the walls of the injured heart.
下一个问题是：这种新的肌肉会与心脏的其他部分同步跳动吗？要回答这个问题，我们回到了含有水母基因的细胞。我们基本上就把这些细胞当做太空探测器一样来使用，我们把它们放到一个陌生的环境中，然后我们通过返还给我们的闪烁信号，来了解它们的生物活性。你们现在看到的是一个放大的豚鼠心脏的黑白图像，这颗心脏受了伤，然后接受了三轮的人体心肌移植。你们可以看到那些斜行的白线。每个都是针线，里面有几百万人类心肌细胞。当我开始放视频的时候，你们就可以看到我们透过显微镜时看到的景象。细胞在闪烁，而且它们在同步闪烁，透过受伤的心脏壁传回来。
08:03
What does this mean? It means the cells arealive, they're well, they're beating, and they've managed to connect with oneanother so that they're beating in synchrony. But it gets even more interestingthan this. If you look at that tracing that's along the bottom, that's theelectrocardiogram from the guinea pig's own heart. And if you line up theflashing with the heartbeat that's shown on the bottom, what you can see isthere's a perfect one-to-one correspondence. In other words, the guinea pig'snatural pacemaker is calling the shots, and the human heart muscle cells arefollowing in lockstep like good soldiers.
这是什么意思？这意味着细胞是活的，它们很好，它们在跳动，它们已经成功的融为一体了，所以它们在同步跳动。但还有更有意思的事情。如果你看底部的线条，这是豚鼠心脏的心电图。如果你把闪光和心跳排成一行如图所示，你看到的是一对一的完美对应。换言之，豚鼠自身的心脏正在主导，而人体心肌细胞则是亦步亦趋的跟随着，就像好士兵一样。
08:37
(Applause)
（掌声，欢呼）?
08:44
Our current studies have moved into what Ithink is going to be the best possible predictor of a human patient, and that'sinto macaque monkeys. This next slide shows you a microscopic image from theheart of a macaque that was given an experimental heart attack and then treatedwith a saline injection. This is essentially like a placebo treatment to showthe natural history of the disease. The macaque heart muscle is shown in red,and in blue, you see the scar tissue that results from the heart attack. So asyou look as this, you can see how there's a big deficiency in the muscle inpart of the wall of the heart. And it's not hard to imagine how this heartwould have a tough time generating much force.
我们目前的研究已经进入了我所认为的和人类最相近的动物实验阶段，那就是猕猴实验。下一张幻灯片是一幅显微图像，展示了一只实验性心脏病发作的猕猴心脏，然后被注射了盐水。这基本上就像安慰剂治疗，显示疾病的自然发生过程。猕猴的心肌呈红色，蓝色部分，你可以看到心脏病引起的疤痕组织。当你看着这张图时，你会发现心室壁的一部分?肌肉有很大的缺陷。不难想象这颗心脏在起搏时会有多么大的阻碍。
09:25
Now in contrast, this is one of the stem-cell-treatedhearts. Again, you can see the monkey's heart muscle in red, but it's very hardto even see the blue scar tissue, and that's because we've been able torepopulate it with the human heart muscle, and so we've got this nice, plumpwall.
相反，这是颗接受干细胞治疗的心脏。同样的，你可以看到猴子的心肌是红色的，但是很难看到蓝色的疤痕组织，那是因为我们用了人类的心肌?去恢复了它，所以我们重新有了一扇漂亮丰满的心室壁。
09:43
OK, let's just take a second and recap.I've showed you that we can take our stem cells and differentiate them intocardiac muscle. We've learned how to keep them alive after transplantation,we've showed that they beat in synchrony with the rest of the heart, and we'veshown that we can scale them up into an animal that is the best possiblepredictor of a human's response. You'd think that we hit all the roadblocksthat lay in our path, right? Turns out, not.
好吧，让我们花点时间回顾一下。我已经向你展示了我们的干细胞以及它们分化成心肌细胞的过程。我们已经学会了如何在移植后保持它们的活力，我们已经证明它们与心脏的其他部分同步跳动，我们已经证明我们可以在成为最能预测人类反应的动物身上进行实验。你们会认为我们清除了所有阻碍我们前进的路障，对吧？事实证明，不是这样。
10:12
These macaque studies also taught us thatour human heart muscle cells created a period of electrical instability. Theycaused ventricular arrhythmias, or irregular heartbeats, for several weeksafter we transplanted them. This was quite unexpected, because we hadn't seenthis in smaller animals. We've studied it extensively, and it turns out that itresults from the fact that our cellular graphs are quite immature, and immatureheart muscle cells all act like pacemakers. So what happens is, we put theminto the heart, and there starts to be a competition with the heart's naturalpacemaker over who gets to call the shots. It would be sort of like if youbrought a whole gaggle of teenagers into your orderly household all at once,and they don't want to follow the rules and the rhythms of the way you runthings, and it takes a while to rein everybody in and get people working in acoordinated fashion. So our plans at the moment are to make the cells gothrough this troubled adolescence period while they're still in the dish, andthen we'll transplant them in in the post-adolescent phase, where they shouldbe much more orderly and be ready to listen to their marching orders. In themeantime, it turns out we can actually do quite well by treating withanti-arrhythmia drugs as well.
这些猕猴的研究也教会了我们，我们人类的心肌细胞造成了一段时间的心电不稳。它们引起了室性心律失常或不规则的心跳，长达移植后几个星期之久。这完全出乎意料，因为我们在小动物身上没有看到过。我们对这进行了广泛的研究，结果发现，发生的原因是我们的细胞图很不成熟，未成熟的心肌细胞都像起搏器。所以当我们把它们放进心脏，它们便开始与心脏的自然起搏竞争决定谁来占主导地位。这就有点像如果你一下子把一群傻乎乎的青少年带到你井然有序的家里，他们不想遵守你的规则和节奏，需要一段时间来控制所有人，让人们以协调一致的方式工作。所以我们现在的计划是当细胞还在培养皿里的时候，让它们经历这个麻烦的“青春期”，然后我们在“青春期”后移植它们，那时它们会更加的有序，准备好遵守它们的行军命令。同时，事实证明当这种方法和抗心律失常药物结合时，我们做的相当不错。
11:27
So one big question still remains, and thatis, of course, the whole purpose that we set out to do this: Can we actuallyrestore function to the injured heart? To answer this question, we went tosomething that's called "left ventricular ejection fraction."Ejection fraction is simply the amount of blood that is squeezed out of thechamber of the heart with each beat. Now, in healthy macaques, like in healthypeople, ejection fractions are about 65 percent. After a heart attack, ejectionfraction drops down to about 40 percent, so these animals are well on their wayto heart failure. In the animals that receive a placebo injection, when we scanthem a month later, we see that ejection fraction is unchanged, because theheart, of course, doesn't spontaneously recover. But in every one of theanimals that received a graft of human cardiac muscle cells, we see asubstantial improvement in cardiac function. This averaged eight points, sofrom 40 to 48 percent. What I can tell you is that eight points is better thananything that's on the market right now for treating patients with heartattacks. It's better than everything we have put together. So if we could doeight points in the clinic, I think this would be a big deal that would make alarge impact on human health.
还有一个大问题，当然，这就是我们开始做这件事的全部目的：我们真的能恢复受伤心脏的功能吗？要回答这个问题，我们研究了所谓的“左心室射出分率”。射出分率是每一次起搏时从心腔中挤出来的血液量。健康的猕猴，就像健康人一样，射出分率约为65%。心脏病发作后，射出分率下降到40%左右，所以这些动物很快就会患上心力衰竭。在接受安慰剂注射的动物中，一个月后当我们扫描它们时，我们看到射出分率不变，因为心脏不会自动恢复。但是在每只接受人体心肌细胞移植的动物身上，我们看到心脏功能有了实质性的改善。从40%到48%，平均有8个点的提升。我能告诉你的是8个点比现在市场上的任何用于治疗心脏病患者的东西都要好。这和我们把所有的东西放在一起比都要好。如果我们能在临床上达到8个点，我认为这将会对人类健康产生很大的影响。
12:39
But it gets more exciting. That was justfour weeks after transplantation. If we extend these studies out to threemonths, we get a full 22-point gain in ejection fraction.
但是还有更令人兴奋的。这只是移植后的四周。如果我们把这些研究延长到三个月，射出分率会增长22个点。
12:52
(Applause)
（掌声，欢呼）
12:59
Function in these treated hearts is so goodthat if we didn't know up front that these animals had had a heart attack, wewould never be able to tell from their functional studies.
这些治疗过的心脏功能很好以至于如果我们事先不知道这些动物有过心脏病发作，我们永远无法从功能研究中将它们辨别出来。
13:12
Going forward, our plan is to start phaseone, first in human trials here at the University of Washington in 2020 -- twoshort years from now. Presuming these studies are safe and effective, which Ithink they're going to be, our plan is to scale this up and ship these cellsall around the world for the treatment of patients with heart disease. Giventhe global burden of this illness, I could easily imagine this treating amillion or more patients a year.
接下来，我们的计划是开始第一阶段，2020年首次在华盛顿大学进行人体试验——两年后。假设这些研究是安全有效的，我觉得它们是这样的，我们的计划是扩大规模，把这些细胞运到世界各地用于治疗心脏病患者。鉴于这种疾病的全球性负担，我可以很容易地想象，每年治疗一百万或更多的病人。
13:40
So I envision a time, maybe a decade fromnow, where a patient like my mother will have actual treatments that canaddress the root cause and not just manage her symptoms. This all comes fromthe fact that stem cells give us the ability to repair the human body from itscomponent parts.
我设想一个时间，也许十年后，像我母亲这样的病人会接受真正的治疗，这可以解决根本原因，而不仅仅是缓解她的症状。这些都因为干细胞让我们有能力可以从人类身体的组成部分来修复自身。
13:58
In the not-too-distant future, repairinghumans is going to go from something that is far-fetched science fiction intocommon medical practice. And when this happens, it's going to have atransformational effect that rivals the development of vaccinations andantibiotics.
在不久的将来，修复人类就要从牵强附会的科幻小说中走进普通的医学实践。当这发生时，它会产生一个颠覆性的效果，可以比肩疫苗和抗生素的发展。
14:18
Thank you for your attention.
谢谢你们的聆听。
14:19
(Applause)
（掌声，欢呼）
