What if I told you that the pandemic will save the lives of millions of people? It's a difficult thing to consider, given how many loved ones we've already lost. But throughout the course of human history, massive public health crises have resulted in innovation in health care and technology. For example, the Black Death gave rise to the Gutenberg press and the 1918 flu pandemic led to modern vaccine technology. The COVID-19 pandemic has and will be no different. Just look at our vaccines -- normally developed over many years, and the mRNA vaccines were deployed in a mind-blowing 11 months.
如果我跟你说这场疫情将会 拯救无数人的性命,你相信吗? 这很难想象, 鉴于我们已经失去了 这么多挚爱之人。 但是,在人类历史进程中, 大范围的公共卫生危机 是推动医疗保健和科技创新的契机。 比如,黑死病使得 古腾堡印刷机得以流行, 1918 年的大流感 推动了现代疫苗技术的发展。 新冠疫情亦如是。 以疫苗为例, 通常需要多年才能研发出来, 而mRNA疫苗令人興奮地 在短短的 11 个月内就得以上市。
How is that even possible? It was possible because scientists have been working for many years to get us to the point where we could use mRNA quickly in an emergency situation. Specifically, we've been working on how to help mRNA with its biggest problem, which is that it doesn't normally go to the right places inside of our bodies. Fortunately, we got around that problem just in time, and I'd like to tell you about the technology that we use to do it.
这怎么可能? 是因为科学家此前 已经钻研了很多年, 我们才得以在这么紧急的情况下 迅速运用mRNA技术。 具体而言, 我们已经在mRNA如何攻克 其最大的问题上研究多年, 这个问题就是它通常 无法抵达我们体内正确的位置。 幸运的是, 我们及时解决了这个问题, 我想和大家分享 我们解决问题的这项技术。
When mRNA is administered, it's injected into our muscles or our bloodstream, but we actually need it to go inside of our cells. Unfortunately, mRNA is fragile, and our bodies will destroy it before it goes very far. You can think of mRNA like a glass vase that you'd like to send in the mail without a box and bubble wrap. It'll break long before it's been delivered. And without an address on the box, your postal delivery service will have no idea where to take it. And so if we're going to use mRNA as a therapeutic, it needs our help. It needs protection, and it needs to be told where to go. And that's where I come in.
使用mRNA时, 它会通过肌肉注射, 进入体内循环的血液, 但我们真正需要的是 让它进入我们的细胞中。 很不幸的是,mRNA非常脆弱, 而我们的身体会在 它没移动多远之前就摧毁它。 你可以把mRNA想象成 邮寄一只玻璃花瓶, 如果没有防震膜和盒子, 它在送达之前早就碎了。 而且如果盒子上没有地址, 邮政服务系统根本不知道往哪儿送。 所以,如果我们要 把mRNA当作治疗手段, 就需要人为介入。 除了防护装置, 它还需要知道往哪儿移动。 这也就是我研究的领域。
For over five decades, scientists and engineers like myself have been creating the shipping materials for nucleic acid drugs, like DNA and RNA. Through trial and error, we've created packages that deliver intact vases to the wrong address; that delivered to the right address but with a broken vase; packages that get ripped apart by attacking dogs; and packages that throw out the mail carrier's back. It's taken many years to get the science right. Let me show you the result, these tiny balls of fat that we call lipid nanoparticles. Let me tell you what they are and how they work.
在过去五十年间, 和我一样的科学家和工程师 一直致力于为核酸药物创造载体, 如DNA和RNA。 通过试错,我们创造出了 可以把花瓶完好无损地 送去错误地址的载体; 或者地址对,但花瓶却破损的载体; 被看门狗扯坏了的载体; 或者从邮递员的背包 掉了出去的载体。 总之,我们花了很多年 才把它搞明白。 给大家看一下这个结果, 这些我们称之为脂质纳米粒 (lipid nanoparticles)的微小脂肪球, 请听我细细道来 它们是啥,有什么用。
So first of all, "nano" just means really, really small. Think of how small a person is compared to the diameter of the earth. That's how small a nanoparticle is compared to the person. These nanoparticles are made up of several fatty molecules called lipids. Fat is an awesome packing material -- nice and bouncy. Interestingly, our cells are also surrounded by fat to keep them flexible and protected. Years ago, scientists had the idea to create lipid nanoparticles that would act like a Trojan horse. Because the lipids in the nanoparticle look similar to the membranes that surround our cells, the cells are willing to bring the nanoparticle inside, and that's when the mRNA is released into the cell. So what, exactly, are the lipids in these nanoparticles? There are four ingredients in addition to the mRNA, and I'll tell you about each one.
首先,纳米就意味着非常非常小。 想像一下一个人和地球的直径比较 是多么渺小的存在。 同样的道理,一个纳米颗粒 和人体比起来也是非常渺小的。 这些纳米颗粒由无数 称作脂质的脂肪分子组成。 脂肪是非常优秀的包裹材料, 又好又有弹性。 有趣的是,我们的细胞 同样由脂肪包裹, 以确保其弹性和受保护。 很多年以前,科学家们突发奇想, 创造出如同特洛伊木马 一样的脂质纳米粒。 由于在纳米颗粒中的脂质 与包裹在我们细胞表层的膜相似, 细胞对纳米颗粒不排斥, 而这就是mRNA侵入细胞的时机。 那么,在这些纳米颗粒中的脂质 到底是什么呢? 除了mRNA之外,还有四种成分, 接下来我会分别告诉你。
First, there's a lipid called a phospholipid. This is the primary ingredient in our cell membranes, which are the walls of fat that separate the insides of our cells from everything that surrounds them. Phospholipids have a head that likes water and a tail that likes other fatty things. So when you throw a bunch of phospholipids together in water, they form this beautiful structure called a lipid bilayer. Here, the heads face the inside and the outside of the cell, which is water, and the fat-loving parts of the molecule hang out together in the middle. In lipid nanoparticles, phospholipids have a similar role of keeping all of the other ingredients organized.
首先,有一类叫做 磷脂(phospholipid)的脂质。 这是我们细胞膜的主要成分, 即脂肪壁,用来将细胞内液 与其周围的其他物质分隔开来。 磷脂的顶端亲水, 尾端则亲脂。 因此,如果将一堆磷脂投入水中, 会迅速形成这一叫做双层脂膜 (lipid bilayer)的精美结构体。 这里(双层脂膜分子的)顶端朝内, (面对着)细胞外部的水, 而分子中亲脂的部分聚集在中间。 在脂质纳米粒中, 磷脂也有类似的作用, 将其他所有成分有序地整合在一起。
Second, there's a lipid called cholesterol. Why, if cholesterol has a bad reputation, would we want to use it in a therapeutic nanoparticle? It turns out that while cholesterol can be bad when it's in our bloodstream, it's actually a really good thing for our cell membranes. And that's because those phospholipids I just told you about, they are entirely too free with themselves, and they are prone to falling apart. Cholesterol is a stiff molecule that wedges itself in between the other lipids to fill in the gaps and hold them all together. It plays a similar role in our lipid nanoparticles. It provides structural support so the nanoparticles don't fall apart in between the injection and when they get into our cells.
第二,有一种脂类叫做胆固醇。 既然胆固醇的名声这么差, 我们会想将其用于 治疗用的纳米颗粒中吗? 事实上,虽然血管中存在的 胆固醇对我们有害, 它对细胞膜其实是 非常有益的。 也就是因为我刚跟大家提到的磷脂, 它们互相之间疏离得很, 也很容易分散。 胆固醇是种刚性分子, 夹在其他脂类中间, 填补空隙并将其维持在一起。 其在脂质纳米粒的作用类似。 它为纳米粒提供支撑结构, 以防止其在注射 和进入细胞之间分散。
Third, there's a lipid called an ionizable lipid. Here, "ionizable" means that when these particles are in the bloodstream, they're neutrally charged, which helps with their safety. Then they switch to a positive charge inside of our cells, which helps them release the mRNA. Ionizable lipids are special because they have to be made in the lab, and scientists around the world have tested tens of thousands of these materials to find ones that are good at delivering mRNA safely. And because they're made in the lab, they tend to be proprietary to the company that invented them. So, for example, Moderna and BioNTech, the company that partnered with Pfizer, they discovered different ionizable lipids, and that is the only important ingredient in their COVID-19 vaccines that differ. And even then, their ionizable lipids aren't even that different, which is reassuring, because when independent groups of scientists converge on similar solutions, it's easier to trust the result.
第三,有一类脂质叫做 可电离脂质(ionizable lipid)。 这里的“可电离”指的是 当这些颗粒进入血管中, 它们会变成中性粒子, 以确保其无害。 然后在细胞中转变成正电荷, 以帮助其释放mRNA。 可电离脂质的特别之处 在于它们是在实验室合成的, 全世界的科学家们 为了找到那些可以 安全搭载mRNA的脂质材料 已经进行了成千上万次试验。 也正因为其在实验室合成, 它们往往是发明公司的专利。 因此,比如莫德纳(Moderna),以及 与辉瑞(Pfizer)的合作公司BioNTech, 两者发现了不同的可电离脂质, 这是两者的新冠疫苗 唯一的主要差异成分。 即便如此,两者的可电离脂质 差异并不怎么大, 这一点还挺能让人放心, 因为互相独立研究的科学家们 达成了类似的解决方案, 其结果更加容易让人信服。
Finally, one more ingredient. This one is a polymer called polyethylene glycol. So let's call it PEG. That's much easier. PEG is a water-loving molecule. So it surrounds the lipid nanoparticle and it holds it all together. You can think of the other three lipids as the box and the bubble wrap for the mRNA, and the PEG as the packing tape. You may have heard in the news about a tiny fraction of people that have allergic responses to the vaccine. There is some evidence that PEG could be contributing to these allergic reactions. And that's because people are routinely exposed to PEG in cosmetic and household products, and some people have already developed antibodies against PEG. But why would this happen to some people and not to others? It turns out that every person's immune system is different, and just the same way that some people are allergic to latex, other people are allergic to PEG. It's important to keep in mind, however, that PEG has had a long history of safe use as part of FDA-approved drug formulations, and these vaccine allergies could be caused by things other than PEG. More research is needed to get to the bottom of these side effects.
最后,还有一种成分, 是一种聚合物, 叫做聚乙二醇(polyethylene glycol)。 我们就称其为PEG吧, 这样简单些。 PEG是一种亲水分子。 PEG包裹着脂质纳米粒, 把它聚集起来固定住。 你可以想象成其他三种脂质 是mRNA的包装盒和缓冲垫, 而PEG是封箱带。 大家可能在新闻里听说了一小部分人 对疫苗有过敏反应。 这里有些PEG 导致过敏反应的证据。 由于人们普遍在 化妆品和家用产品中接触过PEG, 并且有些人已经对其产生抗体。 那为什么有些人有这种反应, 其他人却没有呢? 事实证明是因为每个个体的 免疫系统的差异, 就像有的人对乳胶过敏, 有的人对PEG过敏。 记住这点很重要。 但是,PEG作为美国食药监局 (FDA)认证的药物配方成分, 其使用的安全性 不是一天两天得来的, 并且这对于疫苗的过敏反应 可能是由其它物质造成的。 为了确定这一副作用的根本原因, 需要做更深入的调查。
All right, so let's take a step back and look at our whole nanoparticle. Beautiful, right? When these ingredients all fit together nicely, the result is a deliverywoman's dream. In the case of the vaccines, after these nanoparticles get injected into our muscle, they take the mRNA into our cells. There, the mRNA acts like an instruction manual that tells our cells to make a foreign protein, in this case, the coronavirus spike protein. When our immune cells see the spike protein, they rush to protect us from it, and they teach themselves to remember it, so that they can kill it if it ever returns. As we speak, the mRNA vaccines are out there saving lives from the coronavirus. They were our first and best tool to combat this nightmare, and they are our best hope of responding swiftly to viral variance because we can keep our lipid nanoparticle packaging the same, and all we have to do is swap out the mRNA that's inside.
那么,让我们退一步看看 我们整个纳米粒。 很美,对不对? 当这些成分很好地结合在一起时, 结果感人。 至于疫苗, 当这些纳米粒注射进我们的肌肉, 它们把mRNA带入我们的细胞中。 然后, mRNA作为信使, 通知我们的细胞 为防御外敌入侵做准备。 在这里,就是冠状病毒纤突蛋白。 当我们的免疫细胞 发现了纤突蛋白, 就会保护我们免受其扰, 并通过记住这些外敌, 在其杀回马枪时置之于死地。 就在我们话语间, mRNA疫苗一直在 抵御新冠病毒,拯救生命。 它们是我们打赢这场战役的 第一个也是最好用的武器, 它们也是我们快速应对 病毒变异的最好手段, 因为我们不用替换 脂质纳米粒这一载体, 只需替换其内部的 mRNA即可。
But here's the best part: for mRNA therapeutics, these vaccines are only the beginning. mRNA can be used to treat or cure many diseases. So in the future, we will likely have treatments for many terrible diseases, including cystic fibrosis, muscular dystrophy and sickle cell anemia. These diseases are caused by mutated proteins, and we can use mRNA to ask our cells to make the correct version of these proteins. We'll have treatments for cancer -- breast, blood, lungs -- you name it. Here, we'll use mRNA to teach our immune cells how to find and kill cancer cells. And then, if we're lucky, we'll have vaccines against some of the most deadly and feared pathogens across the globe, including malaria, Ebola and HIV. Some of these products are already in clinical trials, and the success of the COVID-19 vaccines will pave the way for future generations of these therapies.
这是最重要的一点: 对于mRNA疗法而言, 这些疫苗仅仅是个开端。 mRNA可以被用来 治愈许多其他疾病。 因此,在将来我们很有可能 可以治愈许多恶疾, 比如囊胞性纤维症、 肌肉萎缩症、 以及镰状细胞性贫血等。 这些疾病是由突变的蛋白质引起的, 我们可以通过mRNA 使细胞自行修正其蛋白质。 我们能治愈乳腺癌、 血癌、肺癌等等。 我们可以使用mRNA片段 培育免疫细胞, 寻找和杀死癌症细胞的方法。 然后,如果我们幸运的话, 我们就能研发出对抗全球 最致命的可怕病原体疫苗, 比如,疟疾、埃博拉病毒和艾滋病。 有一些产品其实已经在临床试验, 而新冠疫苗的成功 为这些疗法的未来迭代打下了基础。
This is how the pandemic will save the lives of millions. It catalyzed the most rapid vaccine development in history and brought to life a niche, previously unapproved form of technology. And in our desperation, we gave that technology a chance. Now we're collecting long-term safety and efficacy data from hundreds of millions of people. And with these data, interest in the technology, funding for the technology and trust in the technology will continue to grow.
这就是这次疫情 拯救成千上万人命的方法。 它推动了人类历史上 最迅速的疫苗开发, 并实现了一种以前未经批准的、 有商机的技术形式。 在绝望中,我们给了 这一技术一个机会。 如今,我们从成千上万的人们身上 收集着长期安全有效的数据。 通过这些数据, 对这一技术的热忱、 投资、 和信任, 将源源不断。
Looking ahead, the packaging and delivery of mRNA to the right organs and tissues will continue to be one of the most significant challenges to implementing this technology. And so my colleagues and I are going to be busy for a very long time. Ultimately, I'm here with a message of hope. We are on the cusp of a revolution. mRNA is about to change the world forever, and it's all thanks to these fatty little balls that take this miracle medicine to exactly where it's needed.
展望未来, 将mRNA包装运输到 正确的器官和组织这一课题 仍将是实施这一技术 最重要的挑战之一。 因此我将和我的同事们一起 继续忙很长一阵。 最后,我想传递希望。 我们正处在一场革命的风口浪尖, mRNA即将永远改变世界, 这一切都要多亏了 这些小小的脂肪球, 是它们将这神药带来人间。
Thank you.
谢谢。
(Applause)
(掌声)