So let me ask for a show of hands. How many people here are over the age of 48? Well, there do seem to be a few.
请大家举手告诉我, 这里有多少人已经超过48岁了? 哦,看起来的确有一些。
Well, congratulations, because if you look at this particular slide of U.S. life expectancy, you are now in excess of the average life span of somebody who was born in 1900.
那么,恭喜, 因为如果你们看看这张关于美国人寿命期望的幻灯片, 你们现在已经超过了1900年生人的 寿命的平均值。
But look what happened in the course of that century. If you follow that curve, you'll see that it starts way down there. There's that dip there for the 1918 flu. And here we are at 2010, average life expectancy of a child born today, age 79, and we are not done yet. Now, that's the good news. But there's still a lot of work to do.
但是看看这个世纪发生的事情, 看这条曲线, 你会发现在这里开始下降了。 那是因为1918年的流感 这里是2010年的数据 这一年出生的婴儿的平均寿命期望是79岁, 而且这一数值还在继续增长。 这当然是个好消息。 但是我们仍有很多事情可以做。
So, for instance, if you ask, how many diseases do we now know the exact molecular basis? Turns out it's about 4,000, which is pretty amazing, because most of those molecular discoveries have just happened in the last little while. It's exciting to see that in terms of what we've learned, but how many of those 4,000 diseases now have treatments available? Only about 250. So we have this huge challenge, this huge gap.
例如,如果你问, 我们已经发现了多少种 由分子层面引起的疾病? 结果是大约4000种,这真的很惊人。 因为这些疾病中的大多数, 都是在最近才被发现的。 对于迄今为止的成果我们当然很兴奋 但是这4000种疾病中, 现在有多少种可以被有效治疗? 大概只有250种。 所以我们面临着巨大的挑战,这是个很可观的差距。
You would think this wouldn't be too hard, that we would simply have the ability to take this fundamental information that we're learning about how it is that basic biology teaches us about the causes of disease and build a bridge across this yawning gap between what we've learned about basic science and its application, a bridge that would look maybe something like this, where you'd have to put together a nice shiny way to get from one side to the other.
你可能认为这不会很难, 我们应该有能力 运用我们学到的 基础生物学知识 去搞明白这些疾病的成因 然后把差距的两端用一座“桥”连接起来 一端是我们所学的基础科学, 一端是这些理论的实际应用。 这个桥看起来可能是这样的, 一条光辉的康庄大道, 从这一端连接到另一端。
Well, wouldn't it be nice if it was that easy? Unfortunately, it's not. In reality, trying to go from fundamental knowledge to its application is more like this. There are no shiny bridges. You sort of place your bets. Maybe you've got a swimmer and a rowboat and a sailboat and a tugboat and you set them off on their way, and the rains come and the lightning flashes, and oh my gosh, there are sharks in the water and the swimmer gets into trouble, and, uh oh, the swimmer drowned and the sailboat capsized, and that tugboat, well, it hit the rocks, and maybe if you're lucky, somebody gets across.
嗯,如果真的这么简单就好了。 很不幸的,没那么简单。 在现实中,从基础的知识到实际应用的连接 看起来更像这样: 根本没有光辉的的桥梁。 你只能近似于盲目地把宝押在不同的途径上 可能你有一名游泳选手,一艘划艇, 一艘帆船和一艘拖船。 你让他们各自出发。 暴风雨来了,电闪雷鸣。 噢天哪,水里还有鲨鱼, 游泳的人遇到了麻烦 糟糕,你的游泳选手淹死了。 帆船翻了, 拖船撞到了岩石, 如果你运气好,有人可能刚好路过。
Well, what does this really look like? Well, what is it to make a therapeutic, anyway? What's a drug? A drug is made up of a small molecule of hydrogen, carbon, oxygen, nitrogen, and a few other atoms all cobbled together in a shape, and it's those shapes that determine whether, in fact, that particular drug is going to hit its target. Is it going to land where it's supposed to? So look at this picture here -- a lot of shapes dancing around for you. Now what you need to do, if you're trying to develop a new treatment for autism or Alzheimer's disease or cancer is to find the right shape in that mix that will ultimately provide benefit and will be safe. And when you look at what happens to that pipeline, you start out maybe with thousands, tens of thousands of compounds. You weed down through various steps that cause many of these to fail. Ultimately, maybe you can run a clinical trial with four or five of these, and if all goes well, 14 years after you started, you will get one approval. And it will cost you upwards of a billion dollars for that one success.
好,真实情况看起来是怎样? 究竟什么东西有疗效? 药是什么?药是由 氢分子,碳分子 氧分子,氮分子和一些其他原子 联结成特定形状的物体, 事实上正是这些形状决定 特定的药能够达到疗效。 会到达它该去的地方吗? 所以,看看这幅图片——很多不同的形状在你周围跳动。 现在你要做的是,如果你试着开发, 自闭症,老年痴呆症, 或者癌症的治愈方法, 就是在那些杂乱中找到对的形状, 哪个能最终带来疗效并且安全的形状。 我们来看看这个过滤管形状的的图示, 刚开始时可能有上千种 甚至上万种的化合物, 需要很多步的过滤 可能很多会失败 最终,其中的四五种药可能可以用于临床试验 如果一切顺利,14年后 其中一个会获得批准。 这可能花费10亿多的美金 就为了这么一个成功。
So we have to look at this pipeline the way an engineer would, and say, "How can we do better?" And that's the main theme of what I want to say to you this morning. How can we make this go faster? How can we make it more successful?
所以我们必须以工程师的方式看着这个过程 然后发问,“要怎么做才能做得更好呢?” 这就是今天早上我想说的主题, 怎样让这个过程进展更快? 怎样让这个过程的结果更成功?
Well, let me tell you about a few examples where this has actually worked. One that has just happened in the last few months is the successful approval of a drug for cystic fibrosis. But it's taken a long time to get there. Cystic fibrosis had its molecular cause discovered in 1989 by my group working with another group in Toronto, discovering what the mutation was in a particular gene on chromosome 7. That picture you see there? Here it is. That's the same kid. That's Danny Bessette, 23 years later, because this is the year, and it's also the year where Danny got married, where we have, for the first time, the approval by the FDA of a drug that precisely targets the defect in cystic fibrosis based upon all this molecular understanding. That's the good news. The bad news is, this drug doesn't actually treat all cases of cystic fibrosis, and it won't work for Danny, and we're still waiting for that next generation to help him.
让我告诉你们几个例子, 几个其实还真管用的例子。 一个是几个月前刚发生的, 一种治疗囊性纤维化的药物成功通过了审批。 它花了很长的时间才最终到达这一步。 囊性纤维化的分子层面的成因在1989年被 我的小组和另一个在多伦多的小组一起合作发现, 我们发现突变发生在7号染色体上的。 一个特定基因上 看到那张照片了吗? 看这里,他们是同一个人。 那是23年后的Danny Bessette。 在这一年 这也是Danny结婚的一年 我们第一次获得FDA的批准, 一种药物可基于对所有这些分子的理解 精准修复囊性纤维化的缺陷。 这是好消息。 坏消息是这个药并不能真正治疗所有的囊性纤维化 它对Danny也无效,我们仍然在等待 能够真正帮助他的下一代产品。
But it took 23 years to get this far. That's too long. How do we go faster?
这经历23年才有这样的成效,非常久的时间。 怎么样才能更快?
Well, one way to go faster is to take advantage of technology, and a very important technology that we depend on for all of this is the human genome, the ability to be able to look at a chromosome, to unzip it, to pull out all the DNA, and to be able to then read out the letters in that DNA code, the A's, C's, G's and T's that are our instruction book and the instruction book for all living things, and the cost of doing this, which used to be in the hundreds of millions of dollars, has in the course of the last 10 years fallen faster than Moore's Law, down to the point where it is less than 10,000 dollars today to have your genome sequenced, or mine, and we're headed for the $1,000 genome fairly soon. Well, that's exciting. How does that play out in terms of application to a disease?
一种方法是用利用技术。 其中一个我们非常重要的技术 就是人类基因组, 能够找出一条染色体, 解密它,分离所有的DNA, 并能够解读出其中的DNA密码的能力 那些A,C,G 和 T 核苷酸 这是人体说明书,也是所有有生命物体的说明书。 这项工作的花费, 曾经需要几亿美元。 但在过去的十年里, 它以比摩尔定律更快的速度下降, 现在用不到一万美元就能做一份关于你我的基因组的测定 并且这个价格很快就能降低到一千美元。 的确很振奋人心。 那么如果应用到疾病治疗中呢?
I want to tell you about another disorder. This one is a disorder which is quite rare. It's called Hutchinson-Gilford progeria, and it is the most dramatic form of premature aging. Only about one in every four million kids has this disease, and in a simple way, what happens is, because of a mutation in a particular gene, a protein is made that's toxic to the cell and it causes these individuals to age at about seven times the normal rate.
我想告诉你们另外一种疾病。 一种非常罕见的紊乱症。 它被称作早年综合衰老症(Hutchinson-Gilford progeria) 这是早衰的最戏剧性方式。 大概四百万分之一的小孩会得这种疾病。 简单说来,其实实际情况就是: 因为某个特定的基因突变, 产生一种对细胞有害的蛋白质, 这对蛋白质造成这些个体衰老。 速度大概是正常衰老速度的七倍。
Let me show you a video of what that does to the cell. The normal cell, if you looked at it under the microscope, would have a nucleus sitting in the middle of the cell, which is nice and round and smooth in its boundaries and it looks kind of like that. A progeria cell, on the other hand, because of this toxic protein called progerin, has these lumps and bumps in it. So what we would like to do after discovering this back in 2003 is to come up with a way to try to correct that. Well again, by knowing something about the molecular pathways, it was possible to pick one of those many, many compounds that might have been useful and try it out. In an experiment done in cell culture and shown here in a cartoon, if you take that particular compound and you add it to that cell that has progeria, and you watch to see what happened, in just 72 hours, that cell becomes, for all purposes that we can determine, almost like a normal cell.
让我用一段影片告诉你们细胞发生了什么。 这个正常的细胞,如果你们在显微镜下看, 会看到细胞中间有细胞核。 漂亮的圆形,边缘光滑。 它看起来就像这样。 而另一方面,一个衰老的细胞, 因为这种叫做丙羟木栓酮的有害蛋白质 会在细胞内产生肿块,凸凹不平。 在发现这一现象以后,我们想要做的 从2003年开始, 就是想要找出一个方法试着修正它。 恩再一次的,通过了解分子途径的某些知识, 我们是有可能 从成千上万的化合物中找出一种或许有用的, 然后进行尝试治疗。 培养细胞时的一个实验, 这里用一段卡通来展示。 如果你把特定的化合物, 加入有早衰症的细胞, 看看会发生什么事情。 仅仅在72小时内,那个细胞变得, 我们可以确定,各个方面, 几乎是一个正常的细胞。
Well that was exciting, but would it actually work in a real human being? This has led, in the space of only four years from the time the gene was discovered to the start of a clinical trial, to a test of that very compound. And the kids that you see here all volunteered to be part of this, 28 of them, and you can see as soon as the picture comes up that they are in fact a remarkable group of young people all afflicted by this disease, all looking quite similar to each other. And instead of telling you more about it, I'm going to invite one of them, Sam Berns from Boston, who's here this morning, to come up on the stage and tell us about his experience as a child affected with progeria. Sam is 15 years old. His parents, Scott Berns and Leslie Gordon, both physicians, are here with us this morning as well. Sam, please have a seat.
这挺让人振奋的,但实际在人体上有效吗? 这项研究只花了四年 就从基因被发现到开始临床研究, 再到非常复杂的测试。 你在这看到的这些小孩, 都是参与研究的志愿者 28个孩子, 从照片上你们能看出来 事实上他们是一群非常优秀的年轻人, 但都被这一疾病侵袭。 每个人看起来都很相像。 不再赘言, 我将邀请其中一位,波士顿来的Sam Berns 早上来刚到,马上要来到讲台上 和大家分享有关他 早衰症的经历 Sam现年15岁。他的父母,Scott Berns和Leslie Gordon,. 都是医生,今天也在这里。 Sam,请坐。
(Applause)
(掌声)
So Sam, why don't you tell these folks what it's like being affected with this condition called progeria?
Sam,你能不能告诉大家 身为早衰症患者是什么样的?
Sam Burns: Well, progeria limits me in some ways. I cannot play sports or do physical activities, but I have been able to take interest in things that progeria, luckily, does not limit. But when there is something that I really do want to do that progeria gets in the way of, like marching band or umpiring, we always find a way to do it, and that just shows that progeria isn't in control of my life.
Sam Burns:嗯,早衰症在某些方面限制了我。 我不能运动,不能参加体育活动。 但我还能对事物保持兴趣, 很幸运,早衰症没有限制这个。 但当我真正想做一些会被早衰症影响的事情的时候, 比如加入军乐队或者当裁判的时候, 我们也总能找到方法去做, 只是想告诉大家我的人生并没有被早衰症掌控。
(Applause)
(掌声)
Francis Collins: So what would you like to say to researchers here in the auditorium and others listening to this? What would you say to them both about research on progeria and maybe about other conditions as well?
Francis Collins: 那么你想对今天在这里的 研究者以及其他观众说些什么吗? 你有什么关于早衰症研究的话想对他们说的吗, 或者针对其他的病症的也可以?
SB: Well, research on progeria has come so far in less than 15 years, and that just shows the drive that researchers can have to get this far, and it really means a lot to myself and other kids with progeria, and it shows that if that drive exists, anybody can cure any disease, and hopefully progeria can be cured in the near future, and so we can eliminate those 4,000 diseases that Francis was talking about.
SB:关于早衰症的研究到目前为止 已经有快15年了, 能走到今天,说明研究人员真的有很强的动力 这不管对我还是对其他的患者来说 都是很有意义的 它也表明只要我们有动力 没有不能治愈的疾病 我也希望早衰症也能在不久的将来也可以被治愈。 这样我们我们就能治愈刚才Francis提到的 4000种疾病
FC: Excellent. So Sam took the day off from school today to be here, and he is — (Applause) -- He is, by the way, a straight-A+ student in the ninth grade in his school in Boston. Please join me in thanking and welcoming Sam. SB: Thank you very much. FC: Well done. Well done, buddy. (Applause)
FC:好极了。Sam今天是翘了一天课 来这的,他—(掌声)— 顺便说一下,他在他波士顿的学校 是九年级全A+优等生 请跟我一起来谢谢Sam并且再次欢迎他来这里。 SB:非常谢谢你们。FC:棒极了。棒极了伙计。 (掌声)
So I just want to say a couple more things about that particular story, and then try to generalize how could we have stories of success all over the place for these diseases, as Sam says, these 4,000 that are waiting for answers. You might have noticed that the drug that is now in clinical trial for progeria is not a drug that was designed for that. It's such a rare disease, it would be hard for a company to justify spending hundreds of millions of dollars to generate a drug. This is a drug that was developed for cancer. Turned out, it didn't work very well for cancer, but it has exactly the right properties, the right shape, to work for progeria, and that's what's happened. Wouldn't it be great if we could do that more systematically? Could we, in fact, encourage all the companies that are out there that have drugs in their freezers that are known to be safe in humans but have never actually succeeded in terms of being effective for the treatments they were tried for? Now we're learning about all these new molecular pathways -- some of those could be repositioned or repurposed, or whatever word you want to use, for new applications, basically teaching old drugs new tricks. That could be a phenomenal, valuable activity. We have many discussions now between NIH and companies about doing this that are looking very promising.
关于这个特别的故事, 我想再多说几句,然后试着总结一下 我们怎样才能听到 更多战胜疾病的故事,就像Sam所说的, 还有4000个疾病在等待答案。 你们可能已经注意到这些对早衰症 做临床试验的药品 并不是专为早衰症设计的 这是如此罕见的疾病,对公司来说一个很难 决定花上亿的钱去研发一种药物来对付它。 这种药物本来是研发来对抗癌症的。 结果它对癌症疗效并不太好, 但它有正确的特性和形状 用来治疗早衰症,所以我们也算误打误撞。 如果我们能更系统地操作,那不是很棒吗? 实际上,如果我们能鼓励外那些 有新型药品的公司 使用这些已知对人体安全, 但从未真正成功 治愈他们打算治疗的疾病的药品 现在我们来看看这些新的分子途径—— 有些能被重新定位或被重新利用 不管你想用什么词来定义它,总之进行各种新的应用 基本上是旧药新用。 那会是一项惊人的,有价值的活动。 我们同国家卫生研究所(NIH)和药厂讨论过很多次 这一议题,这看起来非常有前景。
And you could expect quite a lot to come from this. There are quite a number of success stories one can point to about how this has led to major advances. The first drug for HIV/AIDS was not developed for HIV/AIDS. It was developed for cancer. It was AZT. It didn't work very well for cancer, but became the first successful antiretroviral, and you can see from the table there are others as well.
这项计划真的值得你期待 我们可以列举大量的成功案例 关于它如何带来重大发展 比如治疗艾滋病的药物 一开始并非为艾滋病研发的 它是为癌症研发的,叫做AZT。 它对癌症效果不是很好,但成为 首个成功的抗逆转录病毒的药物 然后你们也能在表格中看到其他的一些例子
So how do we actually make that a more generalizable effort? Well, we have to come up with a partnership between academia, government, the private sector, and patient organizations to make that so. At NIH, we have started this new National Center for Advancing Translational Sciences. It just started last December, and this is one of its goals.
那么我们究竟该如何努力推广普及呢? 嗯,我们必须让学术界 政府,私营部门以及病人组织 合伙干这件事 在国家卫生研究所(NIH),我们已经建立了一个新的 国家医学转化中心 它刚刚在去年十二月成立,刚刚谈到的就是它的一个新目标。
Let me tell you another thing we could do. Wouldn't it be nice to be able to a test a drug to see if it's effective and safe without having to put patients at risk, because that first time you're never quite sure? How do we know, for instance, whether drugs are safe before we give them to people? We test them on animals. And it's not all that reliable, and it's costly, and it's time-consuming. Suppose we could do this instead on human cells. You probably know, if you've been paying attention to some of the science literature that you can now take a skin cell and encourage it to become a liver cell or a heart cell or a kidney cell or a brain cell for any of us. So what if you used those cells as your test for whether a drug is going to work and whether it's going to be safe?
让我告诉你们另一件我们能做的事情。 如果我们不用在人体上进行试验 来检测一项药物是否安全有效 那岂不是很棒? 因为第一次总会有风险 我们如何知道,在我们把它拿给病人之前, 药品是否安全?我们进行动物试验。 然而它不是完全可靠,而且所费不赀 并且费时 想象一下如果我们能在人体细胞上进行试验 如果你留意过一些科学文献的话 你可能会知道 你可以用一个皮肤细胞, 培养成一个肝脏细胞, 或者心脏细胞,肾脏细胞,脑细胞 那如果你用这些细胞试验 某种药品是否有效或者是否安全会怎么样呢
Here you see a picture of a lung on a chip. This is something created by the Wyss Institute in Boston, and what they have done here, if we can run the little video, is to take cells from an individual, turn them into the kinds of cells that are present in the lung, and determine what would happen if you added to this various drug compounds to see if they are toxic or safe. You can see this chip even breathes. It has an air channel. It has a blood channel. And it has cells in between that allow you to see what happens when you add a compound. Are those cells happy or not? You can do this same kind of chip technology for kidneys, for hearts, for muscles, all the places where you want to see whether a drug is going to be a problem, for the liver.
这是一张在片型的肺部细胞的照片 这是波士顿的韦斯研究机构(Wyss Institute )制造的模型。 他们所做的,我们继续看下去, 是从个体中提取细胞, 把它们变成肺脏中出现的细胞的类型, 然后他们他们添加各种药物化合物 看会发生什么 检测是有害,还是安全。 你可以看到这块方片甚至会呼吸 它有空气通道和有血液通道 中间有细胞 让你能看到加入一种复合物后会发生的变化 看看这些细胞状态如何 你可以把同样的芯片技术, 应用在肾脏,心脏,肌肉上, 以及任何地方,或者你想知道一种药物, 是否对肝脏有影响
And ultimately, because you can do this for the individual, we could even see this moving to the point where the ability to develop and test medicines will be you on a chip, what we're trying to say here is the individualizing of the process of developing drugs and testing their safety.
最终,因为我们就可以对个体进行试验了, 我们还可以得到这样的观点, 我们完全可以在一个在小方片上的“你”身上“ 进行药物开发与实验。我们想说明的是, 药品研发的过程, 和测试安全性的过程被个人化了
So let me sum up. We are in a remarkable moment here. For me, at NIH now for almost 20 years, there has never been a time where there was more excitement about the potential that lies in front of us. We have made all these discoveries pouring out of laboratories across the world. What do we need to capitalize on this? First of all, we need resources. This is research that's high-risk, sometimes high-cost. The payoff is enormous, both in terms of health and in terms of economic growth. We need to support that. Second, we need new kinds of partnerships between academia and government and the private sector and patient organizations, just like the one I've been describing here, in terms of the way in which we could go after repurposing new compounds. And third, and maybe most important, we need talent. We need the best and the brightest from many different disciplines to come and join this effort -- all ages, all different groups -- because this is the time, folks. This is the 21st-century biology that you've been waiting for, and we have the chance to take that and turn it into something which will, in fact, knock out disease. That's my goal. I hope that's your goal. I think it'll be the goal of the poets and the muppets and the surfers and the bankers and all the other people who join this stage and think about what we're trying to do here and why it matters. It matters for now. It matters as soon as possible. If you don't believe me, just ask Sam.
让我总结一下 我们现在正经历一个非凡的时刻。 对我而言,在国家卫生研究院已经快20年了, 从来没有一个时刻比现在更让人振奋。 我们面对着无穷的潜力。 世界各地的实验室 做出了不计其数的新发现 我们该如何利用它?首先,我们需要资源。 这是高风险,高花费的研究。 但回报是巨大的,不管是在健康事业, 还是在经济效益上。我们要支持它。 其次,我们需要新型的合作关系 在学术界,政府,私有部门 以及病人组织间,跟我刚才提到的一样 然后利用这种关系进行药物再定位 第三,也是最重要的一点,我们需要人才。 我们需要最好的,最有智慧的人才 从不同领域加入我们, 不分年龄,族群 因为现在就是关键时刻,诸位。 这是你们在等待的21世纪生物学 我们可以抓住机会 让它成为某种,事实上 打败疾病的东西。那是我的目标。 我希望这也是你们的目标 我想它也会是诗人和芝麻街居民的目标 冲浪者和银行家的目标 其他所有人的目标 想想我们试着在做的事情, 以及为什么它如此重要。 现在就很重要, 简直迫在眉睫 如果你们不相信我,问问Sam。
Thank you all very much.
非常感谢。
(Applause)
(掌声)