What if I told you that the pandemic will save the lives of millions of people?
如果我告訴你,
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.
這次疫情將拯救上百萬人的 性命,你覺得如何? 這很難想像, 畢竟我們已經失去了 很多我們所愛的人。 但,在人類歷史上, 大規模的公共衛生危機 通常會帶來健康照護 和技術上的創新。 以黑死病為例, 它促成了古騰堡活字印刷術, 還有 1918 年的流感大流行, 促成現代的疫苗技術。 新冠肺炎疫情也不會是例外。 看看我們的疫苗就知道—— 通常需要多年的研發, 這次 mRNA 疫苗到部署出來, 令人興奮地只花了 短短十一個月的時間。
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.
怎麽可能辦到? 能辦到,是因為科學家 已經投入多年的努力, 讓我們已經能做到快速將 mRNA 用在緊急情況中。 明確來説, 我們一直在研究如何解決 mRNA 最大的問題, 也就是:它一般不會抵達 我們體内正確的目的地。 幸運的是,我們即時 避開了這個問題。 我想跟各位分享我們用在此的技術。
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.
給予 mRNA 時, 會把它注射到我們的肌肉或血液中, 但我們其實需要 讓它進入我們的細胞中。 不幸的是,mRNA 很脆弱, 走不了多遠就會被我們的身體消滅。 可以把 mRNA 想成玻璃花瓶, 你要郵寄它, 卻沒有盒子也沒有氣泡布。 遠在送達之前,它早已被打破了。 而且沒有盒子上的地址, 郵政服務也不會知道 該把它送到哪裡去。 所以,如果我們要把 mRNA 用在治療上, 它就需要我們的協助。 需要保護它, 也需要告訴它該要去哪裡。 此時就該我出場了。
For over five decades, scientists and engineers like myself
五十年來,
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.
像我這樣的科學家及工程師 一直在為核酸藥物 創造運送用的包裝材料, 比如 DNA 和 RNA。 透過試誤法, 我們已經創造出一些包裹, 可以把花瓶完好地送達錯誤的地址。 也可以送到對的地址,但花瓶會破。 也有些包裹會被惡犬咬爛, 也有些包裹會從郵差的背包掉出來。 花了非常多年, 才把科學的部分做對。 讓我給各位看看結果, 這些小小的脂肪球, 我們稱為脂質奈米粒子。 讓我來告訴各位它們是什麼, 以及它們怎麼運作。
So first of all, "nano" just means really, really small.
首先,
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.
「奈米」的意思就是非常非常小。 想想和地球的直徑相比, 一個人有多渺小。 和一個人相比時, 奈米粒子也是那麼渺小。 這些奈米粒子是由許多叫做 「脂質」的脂肪分子組成。 脂肪是很棒的包材—— 很好,很有彈性。 有趣的是,我們的細胞 也是被脂肪包圍, 讓細胞具有彈性且受到保護。 數年前,科學家想出一個點子, 創造脂質奈米粒子, 來當作特洛依木馬。 因為奈米粒子中的脂質看起來很像 包圍我們細胞的膜, 因此細胞願意讓奈米粒子進入, 此時就可以把 mRNA 釋放到細胞中。 所以,這些奈米粒子中的 脂質到底是什麼? 除了 mRNA 之外,還有四種成份, 我會一個一個來談。
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,有一種脂質叫做磷脂。 它是細胞膜的主要成份, 細胞膜是種脂肪牆,把細胞的內部 和周圍的一切分隔開來。 磷脂的頭部喜歡水, 尾部則喜歡其他有脂肪的東西。 所以,當你把一堆磷脂 一起丟到水中, 就會形式這種美麗的結構, 叫做磷脂雙層膜。 在這裡,頭部會面向 細胞的內部和外部, 也就是水, 而分子中喜歡脂肪的部分, 就一起待在中間。 在脂質奈米粒子中, 磷脂也扮演類似的角色, 讓所有其他成份能保持井然有序。
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.
再來,有一種脂質叫做膽固醇。 如果膽固醇的名聲這麼不好,為什麼 我們要把它用在 治療性的奈米粒子中? 結果發現,雖然血液中 有膽固醇時會很不好, 它其實對我們的細胞膜相當好。 因為,我剛才談到的磷脂, 它們自己會太過自由, 它們很容易就會散開。 膽固醇是種很硬的分子, 會把它自己卡在其他脂質之間, 補滿空隙,讓它們能結合在一起。 它在我們的脂質奈米粒子中 也扮演類似的角色。 它能提供結構性的支撐, 讓奈米粒子在被注入之後, 進入我們的細胞之前,都不會散開。
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,有一種脂質叫做離子化脂質。 在這裡,「離子化」的意思是 當這些粒子在血液中時, 屬於電中性, 這對它們的安全性有幫助。 接著, 在我們的細胞中, 它們會換成帶正電, 這樣能協助它們釋放 mRNA。 離子化脂質的特別之處在於 它們只能由實驗室製造, 而世界各地的科學家 已經測試過數萬種這類材料, 來找出有哪些能夠 安全地遞送 mRNA。 因為它們是由實驗室製造, 它們的所有權通常屬於 發明它們的公司。 所以,比如,莫德納 及 BNT,也就是和輝瑞合作的公司。 它們發現了不同的離子化脂質, 它們的新冠肺炎疫苗中 就只有這個重要成份是不同的。 且,儘管如此, 它們的離子化脂質也沒有非常不同, 這很令人寬慰, 因為當獨立的科學家團隊 得出的解決方案會趨向類似, 就比較容易信賴這個結果。
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.
最後,還有一種成份。 它是一種聚合物, 叫做聚乙二醇。 咱們就稱它為 PEG,比較簡單。 PEG 是一種很喜歡水的分子。 所以它會圍繞著脂質奈米粒子, 讓它不要散掉。 你可以把另外三種脂質想成是 mRNA 的盒子和氣泡布, PEG 就是打包用的膠帶。 你可能在新聞上看過, 有很低比例的人 對疫苗會有過敏反應。 有一些證據顯示,PEG 可能會促成 這些過敏反應。 那是因為人會例行性地 接觸到 PEG, 在化妝品和家用產品中都有, 有些人已經發展出 對抗 PEG 的抗體。 但為什麼有些人會過敏, 有些人就不會? 結果發現,每個人的 免疫系統都不一樣, 和有些人對乳類過敏同樣的道理, 也有人會對 PEG 過敏。 不過,很重要的是要記住, 安全使用 PEG 的歷史已久, 它是 FDA 核准的 藥品配方的一部分。 而這些疫苗過敏也有可能是 PEG 以外的東西所引起。 還需要做更多研究才能 弄清楚這些副作用。
All right, so let's take a step back and look at our whole nanoparticle.
好,咱們現在退一步,
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.
來看看整個奈米粒子。 很美,對吧? 當這些成份通通都完美結合, 結果就是讓一位 送貨女子的夢想成真。 就疫苗來說, 奈米粒子被注射進我們的肌肉之後, 它們會把 mRNA 帶到我們的細胞裡。 在那裡,mRNA 扮演說明書的角色, 叫我們的細胞去製造 一種外來蛋白質, 在這個例子中, 就是冠狀病毒棘蛋白。 當我們的免疫細胞看到了棘蛋白, 它們會趕來保護我們,對抗棘蛋白, 它們也會教自己記住這種棘蛋白, 當它再次出現時,它們就能殺了它。 此時此刻, mRNA 疫苗正在外頭 對抗冠狀病毒,拯救人命。 它們是我們對抗這場惡夢的 第一個武器,最好的武器, 它們也是我們快速因應 病毒變種的最佳希望, 因為我們可以繼續使用 相同的脂質奈米粒子包裹, 我們只要換掉裡面的 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.
但,最棒的是: 就 mRNA 療法來說, 這些疫苗只是開端。 mRNA 可以用來治療 或治癒許多疾病。 所以,在未來, 我們可能可以治療許多可怕的疾病, 包括囊腫性纖維化、 肌肉萎縮症, 以及鐮刀型紅血球疾病。 造成這些疾病的是突變的蛋白質, 而我們可以用 mRNA 來要求我們的細胞 製造出這些蛋白質的正確版本。 我們將來也能治療癌症—— 乳癌、血癌、肺癌—— 想得到的都行。 在這個應用上, 我們會透過 mRNA 來教我們的免疫細胞 如何找到並殺死癌細胞。 接著,夠幸運的話, 我們還會有疫苗, 對抗全球各地一些 最致命、最讓人懼怕的病原體, 包括瘧疾、伊波拉, 以及人體免疫缺損病毒。 這些產品當中已經有部分 在進行臨床試驗了, 而新冠肺炎疫苗的成功, 也是為未來世代, 幫這些治療方式舖路。
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.
這就是疫情拯救 數百萬人性命的方式。 它催化了史上最快速的疫苗開發, 催生了一個利基, 先前未被承認的技術形式。 在絕望之際, 我們給了那項技術一個機會。 現在我們在收集長期的 安全性和效力資料, 來自數億人的資料。 有了這些資料, 對這項技術的興趣、 給這項技術的資助, 以及對這項技術的信任, 都會持續增長。
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.
至於將來, 包裝並遞送 mRNA 給正確的器官及組織, 仍然會是導入這項技術的 重大挑戰之一。 所以我和我同事將會 忙碌很長的一段時間。 最終,我是要帶給大家 一個希望的訊息。 我們正在革命的關口上。 mRNA 將要永遠改變世界, 全都要感謝這些小小的脂肪球, 將這種奇蹟之藥帶到需要它的地方。
Thank you.
謝謝。
(Applause)
(掌聲)