So, embryonic stem cells are really incredible cells. They are our body's own repair kits, and they're pluripotent, which means they can morph into all of the cells in our bodies. Soon, we actually will be able to use stem cells to replace cells that are damaged or diseased.
胚胎干细胞 非常神奇, 它们像是人体自带的修理包。 胚胎干细胞具有多向分化的特性,也就是说, 它们可以变成人体中的各种细胞。 其实我们很快就能使用干细胞 替代坏死或发生病变的细胞,
But that's not what I want to talk to you about, because right now there are some really extraordinary things that we are doing with stem cells that are completely changing the way we look and model disease, our ability to understand why we get sick, and even develop drugs. I truly believe that stem cell research is going to allow our children to look at Alzheimer's and diabetes and other major diseases the way we view polio today, which is as a preventable disease.
但这不是我今天演讲的内容。 我们正在就干细胞开展 非同寻常的研究工作, 其结果将彻底转变 我们对于疾病的看法、建模的方式、 对于疾病起因的理解 以及我们开发药物的能力。 我坚信,干细胞研究能使我们的下一代 应对老年痴呆症、糖尿病等重大疾病 就像我们现在应对小儿麻痹症一样, 可以找到预防之道。
So here we have this incredible field, which has enormous hope for humanity, but much like IVF over 35 years ago, until the birth of a healthy baby, Louise, this field has been under siege politically and financially. Critical research is being challenged instead of supported, and we saw that it was really essential to have private safe haven laboratories where this work could be advanced without interference. And so, in 2005, we started the New York Stem Cell Foundation Laboratory so that we would have a small organization that could do this work and support it.
干细胞研究这个神奇的领域 对人类而言,蕴涵着无限的希望。 但是干细胞研究正如35年前的体外授精技术, 在第一例试管婴儿Louise诞生之前, 体外授精一直遭受政治和资金方面的压力。 目前,干细胞方面的关键性研究缺少支持,面临挑战, 我们意识到必须建立私密安全的实验室 继续开展这项工作, 使之不受干扰。 因此,我们在2005年 建立了纽约干细胞基金会实验室, 使得我们可以有一个小小的组织 进行相关研究,对其提供支持。
What we saw very quickly is the world of both medical research, but also developing drugs and treatments, is dominated by, as you would expect, large organizations, but in a new field, sometimes large organizations really have trouble getting out of their own way, and sometimes they can't ask the right questions, and there is an enormous gap that's just gotten larger between academic research on the one hand and pharmaceutical companies and biotechs that are responsible for delivering all of our drugs and many of our treatments, and so we knew that to really accelerate cures and therapies, we were going to have to address this with two things: new technologies and also a new research model. Because if you don't close that gap, you really are exactly where we are today. And that's what I want to focus on. We've spent the last couple of years pondering this, making a list of the different things that we had to do, and so we developed a new technology, It's software and hardware, that actually can generate thousands and thousands of genetically diverse stem cell lines to create a global array, essentially avatars of ourselves. And we did this because we think that it's actually going to allow us to realize the potential, the promise, of all of the sequencing of the human genome, but it's going to allow us, in doing that, to actually do clinical trials in a dish with human cells, not animal cells, to generate drugs and treatments that are much more effective, much safer, much faster, and at a much lower cost.
我们很快意识到,医学研究 以及药物和疗法的开发, 正如你所想,都是被大机构主导的。 但是大机构在涉足新领域时, 有时很难跳出其固有模式, 因而看不清事情的重点。 与此同时,学术研究与 制药公司和生物技术之间的鸿沟 却仍在扩大。 但是,要想将所有药物以及很多疗法付诸应用, 恰恰要靠制药公司和生物科技,因此我们意识到, 要想加快疾病的治愈和治疗, 我们必须解决两个问题: 新技术和新的研究模式。 因为如果不填补这一鸿沟, 我们永远都会原地踏步。 这是我今天要讲的内容。 几年来,我们一直都在思考这一问题, 并且列出了一个任务清单, 还发展了一项新技术, 这是一种软硬件, 能够生成数以百万计的干细胞系, 涵盖全球各种基因阵列, 这其实就是创造了我们自身的阿凡达,也就是化身。 我们开发这一技术的原因在于, 我们认为这能发挥人类基金组测序成果的潜能, 使其蕴涵的希望转变为现实, 而且通过这一过程,我们可以在试验皿中 对人体细胞而不是动物细胞进行临床试验, 从而使我们开发的药物和疗法 效果更好、安全性更高、 见效更快、成本更低。
So let me put that in perspective for you and give you some context. This is an extremely new field. In 1998, human embryonic stem cells were first identified, and just nine years later, a group of scientists in Japan were able to take skin cells and reprogram them with very powerful viruses to create a kind of pluripotent stem cell called an induced pluripotent stem cell, or what we refer to as an IPS cell. This was really an extraordinary advance, because although these cells are not human embryonic stem cells, which still remain the gold standard, they are terrific to use for modeling disease and potentially for drug discovery.
我想给大家介绍一下相关的背景, 帮助大家了解来龙去脉。 这是一个非常前沿的领域。 1998年,人类首次发现胚胎干细胞。 仅仅9年之后, 日本的一个研究小组就成功地采集皮肤细胞, 植入强力病毒,对其进行基因重组, 将其转变成一种多能干细胞, 这种干细胞被称为诱导性多能干细胞, 也就是俗称的IPS干细胞。 这项进展极为重要, 因为这种干细胞虽然达不到 人类胚胎干细胞的“金本位”标准, 但是对疾病建模有极大帮助, 对药物发现可能也会有很大意义。
So a few months later, in 2008, one of our scientists built on that research. He took skin biopsies, this time from people who had a disease, ALS, or as you call it in the U.K., motor neuron disease. He turned them into the IPS cells that I've just told you about, and then he turned those IPS cells into the motor neurons that actually were dying in the disease. So basically what he did was to take a healthy cell and turn it into a sick cell, and he recapitulated the disease over and over again in the dish, and this was extraordinary, because it was the first time that we had a model of a disease from a living patient in living human cells. And as he watched the disease unfold, he was able to discover that actually the motor neurons were dying in the disease in a different way than the field had previously thought. There was another kind of cell that actually was sending out a toxin and contributing to the death of these motor neurons, and you simply couldn't see it until you had the human model.
于是,几个月之后,在2008年, 我们的一位科学家在此基础上, 采集了渐冻人症,也就是英国所说的 运动神经元疾病患者的皮肤活组织, 将其变成了IPS干细胞, 也就是我刚才说过的那种干细胞, 随后,他将这些IPS干细胞变成了运动神经元, 也就是在渐冻人症中逐渐死亡的细胞。 因此简单说来,他取了一个健康细胞, 将其变成一个病变细胞, 并且在培养皿中反复再现这一病变过程。 这非常了不起, 因为这是我们第一次使用活人细胞 对疾病进行建模。 而且,这位科学家在观察病变过程时发现, 在这种疾病中,运动神经元的死亡过程 与此前学术界推想的情况并不相同。 其实是有另一种细胞 释放出一种毒素, 促使运动神经元死亡。 之前无法发现这一点, 是因为还没有使用人体细胞建模。
So you could really say that researchers trying to understand the cause of disease without being able to have human stem cell models were much like investigators trying to figure out what had gone terribly wrong in a plane crash without having a black box, or a flight recorder. They could hypothesize about what had gone wrong, but they really had no way of knowing what led to the terrible events. And stem cells really have given us the black box for diseases, and it's an unprecedented window. It really is extraordinary, because you can recapitulate many, many diseases in a dish, you can see what begins to go wrong in the cellular conversation well before you would ever see symptoms appear in a patient. And this opens up the ability, which hopefully will become something that is routine in the near term, of using human cells to test for drugs.
所以真的可以说, 研究人员试图理解疾病起因、 却没有人类干细胞模型, 就像是调查人员试图查明 坠机事故原因、 却找不到黑匣子或飞行记录仪, 他们可以就事故原因提出假设, 但真的没有办法断定 惨剧究竟是怎么发生的。 而干细胞就像是一个研究疾病的黑匣子, 它也创造了空前的机遇。 干细胞真的意义非凡, 因为我们可以在培养皿中再现多种疾病, 可以看到细胞互相接触时出现问题的过程, 其时点可以远远早于 患者出现症状。 这也赋予了我们一种能力, 一种有望在近期内 发展成为常规操作的能力, 那就是在药物测试中使用人体细胞。
Right now, the way we test for drugs is pretty problematic. To bring a successful drug to market, it takes, on average, 13 years — that's one drug — with a sunk cost of 4 billion dollars, and only one percent of the drugs that start down that road are actually going to get there. You can't imagine other businesses that you would think of going into that have these kind of numbers. It's a terrible business model. But it is really a worse social model because of what's involved and the cost to all of us. So the way we develop drugs now is by testing promising compounds on -- We didn't have disease modeling with human cells, so we'd been testing them on cells of mice or other creatures or cells that we engineer, but they don't have the characteristics of the diseases that we're actually trying to cure. You know, we're not mice, and you can't go into a living person with an illness and just pull out a few brain cells or cardiac cells and then start fooling around in a lab to test for, you know, a promising drug. But what you can do with human stem cells, now, is actually create avatars, and you can create the cells, whether it's the live motor neurons or the beating cardiac cells or liver cells or other kinds of cells, and you can test for drugs, promising compounds, on the actual cells that you're trying to affect, and this is now, and it's absolutely extraordinary, and you're going to know at the beginning, the very early stages of doing your assay development and your testing, you're not going to have to wait 13 years until you've brought a drug to market, only to find out that actually it doesn't work, or even worse, harms people.
现在的药物测试法相当麻烦, 要想将一种成功开发的药物推向市场, 平均需要13年,这还仅仅是一种药物, 此外还会产生40亿美元的沉没成本。 而且计划通过这一流程投放市场的药物中, 只有百分之一能够完成这一目标。 你很难想像还有哪个行业, 是你愿意涉足的, 却有这么高的失败率。 这种商业模式非常糟糕, 但它作为一个社会模式的危害可能更大, 因为它牵涉面广,给所有各方都带来很大成本。 因为,我们现在开发药物时, 测试有望成功的合成物时是使用⋯⋯ 我们以前没有使用人体细胞建模, 因此我们一直使用老鼠细胞进行测试, 或者使用其它生物细胞,或者是我们改造的细胞。 但是我们想要治愈的疾病 在这些细胞上未必会显现出来。 大家知道,我们不是老鼠, 但也不能随便找一位活着的患者, 简简单单地取出几个脑细胞或心脏细胞, 然后就到实验室里胡来, 测试一种有望成功的药物。 但是现在有了人类干细胞, 我们就可以为患者创造阿凡达,创造细胞, 不管是活态的运动神经元细胞, 是跳动着的心脏细胞,还是肝细胞, 或者其他类型的细胞, 都可以造来测试药物或有希望的复合物, 测试的对象就是你想要改变的细胞, 这一点现在就可以做到,绝对意义非凡。 而且你从一开始, 从检测的非常早期的阶段就能知道结果, 不会出现等了13年, 终于将一种药物推向市场,结果却发现 这种药物根本没用,甚至对人体有害的情况。
But it isn't really enough just to look at the cells from a few people or a small group of people, because we have to step back. We've got to look at the big picture. Look around this room. We are all different, and a disease that I might have, if I had Alzheimer's disease or Parkinson's disease, it probably would affect me differently than if one of you had that disease, and if we both had Parkinson's disease, and we took the same medication, but we had different genetic makeup, we probably would have a different result, and it could well be that a drug that worked wonderfully for me was actually ineffective for you, and similarly, it could be that a drug that is harmful for you is safe for me, and, you know, this seems totally obvious, but unfortunately it is not the way that the pharmaceutical industry has been developing drugs because, until now, it hasn't had the tools.
但是仅仅观察 几个人或者一小组人的细胞还不够, 因为我们需要退后一步, 综合考虑。 环顾四周,大家就会发现,我们各不相同, 我可能患上的疾病, 例如老年痴呆症或者帕金森氏症, 对我的影响很可能不同于同一疾病 对你的影响。 况且,如果我们都患上了帕金森氏症, 使用同样的药物, 但由于我们的基因构成不同, 我们的治疗结果很可能也不相同。 很有可能一种对我非常见效的药物 对你却毫无效果,反过来, 也有可能一种对你有害的药物对我却很安全。 这一点似乎显而易见, 但很遗憾,这却不是 制药行业一贯用以开发药物的指导思想。 因为直到现在,相关的工具才到位。
And so we need to move away from this one-size-fits-all model. The way we've been developing drugs is essentially like going into a shoe store, no one asks you what size you are, or if you're going dancing or hiking. They just say, "Well, you have feet, here are your shoes." It doesn't work with shoes, and our bodies are many times more complicated than just our feet. So we really have to change this.
因此,我们需要跳出 这种一刀切的思维模式, 我们一直以来开发药物的方法 就像是走进一家鞋店时, 没有人问我们穿多大号, 买鞋是为了跳舞还是爬山, 只知道说:“哦,你们有脚啊,那给你们鞋。” 这样买鞋是行不通的,而我们的身体 又比我们的脚要复杂很多倍。 所以我们必须改变这一做法。
There was a very sad example of this in the last decade. There's a wonderful drug, and a class of drugs actually, but the particular drug was Vioxx, and for people who were suffering from severe arthritis pain, the drug was an absolute lifesaver, but unfortunately, for another subset of those people, they suffered pretty severe heart side effects, and for a subset of those people, the side effects were so severe, the cardiac side effects, that they were fatal. But imagine a different scenario, where we could have had an array, a genetically diverse array, of cardiac cells, and we could have actually tested that drug, Vioxx, in petri dishes, and figured out, well, okay, people with this genetic type are going to have cardiac side effects, people with these genetic subgroups or genetic shoes sizes, about 25,000 of them, are not going to have any problems. The people for whom it was a lifesaver could have still taken their medicine. The people for whom it was a disaster, or fatal, would never have been given it, and you can imagine a very different outcome for the company, who had to withdraw the drug.
在这方面,本世纪初有一个非常悲伤的事例。 当时有一种效果很好的药物,其实是有一类药物, 但其中我要讲的是Vioxx, 对那些因为关节炎而遭受剧烈疼痛的患者来说, 这种药物绝对是根救命稻草, 但很不幸的是,对于另外一个亚型的患者, 这种药物却会引起心脏方面的严重副作用, 有些患者的副作用非常严重, 并最终死于这种副作用。 但是我们来设想一下另一种情形, 如果我们之前能有心脏细胞的各种基因阵列, 并且已经实际测试过这种药物, 在培养皿中实际测试过Vioxx, 知道某一种遗传类型的人会出现 心脏方面的副作用,而另一些遗传亚型 或遗传“鞋号“的人——大约有2万5千个, 不会出现任何问题。 这样的话,那些将Vioxx视为救命稻草的患者 本可以继续使用, 而那些会因Vioxx发生事故甚至丧命的患者, 永远也不会拿到Vioxx的药方。 不难想像,制药公司本来也可以有很不一样的结局, 不需要将Vioxx撤出市场。
So that is terrific, and we thought, all right, as we're trying to solve this problem, clearly we have to think about genetics, we have to think about human testing, but there's a fundamental problem, because right now, stem cell lines, as extraordinary as they are, and lines are just groups of cells, they are made by hand, one at a time, and it takes a couple of months. This is not scalable, and also when you do things by hand, even in the best laboratories, you have variations in techniques, and you need to know, if you're making a drug, that the Aspirin you're going to take out of the bottle on Monday is the same as the Aspirin that's going to come out of the bottle on Wednesday. So we looked at this, and we thought, okay, artisanal is wonderful in, you know, your clothing and your bread and crafts, but artisanal really isn't going to work in stem cells, so we have to deal with this.
由此可见,干细胞技术真的意义非凡, 我们觉得,好吧, 我们要想解决这个问题, 显然需要考虑遗传学的问题, 需要考虑人体细胞测试。 但是,有一个基本问题, 因为现在干细胞系 尽管非同寻常, 究其实质仍然只是成组的细胞, 是靠手工逐个完成的, 每个干细胞系都会耗时好几个月, 无法批量操作,而且由于是靠手工完成, 即使是在最好的实验室, 操作技术也不可能完全稳定。 此外,从事制药工作的人必须知道, 预备周一从瓶子中取出来的阿司匹林 和预备周三取出来的阿司匹林, 必须是一样的。 我们明白这一点,我们想,好吧, 手工制作有时候是件好事, 例如在制作服装、面包和工艺品的时候, 但对于干细胞来说,手工制作实在不适合, 我们必须解决这一问题。
But even with that, there still was another big hurdle, and that actually brings us back to the mapping of the human genome, because we're all different. We know from the sequencing of the human genome that it's shown us all of the A's, C's, G's and T's that make up our genetic code, but that code, by itself, our DNA, is like looking at the ones and zeroes of the computer code without having a computer that can read it. It's like having an app without having a smartphone. We needed to have a way of bringing the biology to that incredible data, and the way to do that was to find a stand-in, a biological stand-in, that could contain all of the genetic information, but have it be arrayed in such a way as it could be read together and actually create this incredible avatar. We need to have stem cells from all the genetic sub-types that represent who we are.
但即便如此,还有一个很大的障碍, 这就还得说回到 人类基因组测序这一话题, 因为我们各不相同, 而人类基因组测序工作 已经揭示出构成人类基因代码的 A、C、G、T全部四种碱基序列。 但是这种代码本身,也就是我们的DNA, 就像计算机代码中的1和0 一样, 必须使用电脑加以识别, 否则就像下载了app应用程序,却还没有智能手机, 我们必须想办法运用生物知识, 解读这种神奇的数据, 而其方法就是 找一个替身,一个生物替身, 替身必须包含所有遗传信息, 但它的基因序列必须排列得 能够整体解读, 这样就建立了一个神奇的阿凡达。 我们需要收集所有遗传亚型的干细胞, 代表我们特性的干细胞。
So this is what we've built. It's an automated robotic technology. It has the capacity to produce thousands and thousands of stem cell lines. It's genetically arrayed. It has massively parallel processing capability, and it's going to change the way drugs are discovered, we hope, and I think eventually what's going to happen is that we're going to want to re-screen drugs, on arrays like this, that already exist, all of the drugs that currently exist, and in the future, you're going to be taking drugs and treatments that have been tested for side effects on all of the relevant cells, on brain cells and heart cells and liver cells.
这就是我们迄今的工作成果, 这是一项自动的技术, 能够生成数以百万计的干细胞系。 按基因阵列排列, 具备强大的平行处理能力。 我们希望这将改变我们发现药物的方式, 而且我认为其最终结果是 我们会希望对药物进行再次筛选, 按照已有的这种基因阵列筛选 目前已有的全部药物。 将来,人们服用的药物 和接受的治疗都将是经过副作用测试的, 测试将涵盖所有相关细胞, 包括脑细胞、心脏细胞和干细胞。
It really has brought us to the threshold of personalized medicine. It's here now, and in our family, my son has type 1 diabetes, which is still an incurable disease, and I lost my parents to heart disease and cancer, but I think that my story probably sounds familiar to you, because probably a version of it is your story. At some point in our lives, all of us, or people we care about, become patients, and that's why I think that stem cell research is incredibly important for all of us. Thank you. (Applause) (Applause)
干细胞技术真的已经使我们 离药物个性化技术近在咫尺。 这种技术已经进入了我们的生活。 我的儿子患有I型糖尿病, 这仍然是一种绝症。 我的父母死于心脏病与癌症, 可是我想,你们可能会觉得我的遭遇听起来有些耳熟, 因为你可能也有过类似的经历。 在我们生命的某些时刻,我们所有人, 或者我们所关心的人,都会患上疾病, 正是因为如此,我认为,干细胞研究 对我们所有人来说都极其重要。 谢谢。(掌声) (掌声)