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KathrynAWhitehead_2021-_可为医学带来革命的小小脂肪球_
What if I told you that the pandemic will save the lives of millions of people? 如果我告诉你,
It's a difficult thing to consider, given how many loved ones we've already lost. 这很难想像, 毕竟我们已经失去了 很多我们所爱的人。
But throughout the course of human history, massive public health crises have resulted in innovation in health care and technology . 但,在人类历史上, 大规模的公共卫生危机 通常会带来健康照护 和技术上的创新。
What if:如果…怎么办? pandemic:adj.(疾病等)全国流行的;普遍的;n.流行性疾病; throughout:adv.自始至终,到处;全部;prep.贯穿,遍及; massive:adj.大量的;巨大的,厚重的;魁伟的; crises:n.危机,紧要关头;危险期(crisis的复数形式); innovation:n.创新,革新;新方法; health care:n.卫生保健; technology:n.技术;工艺;术语;
For example, the Black Death gave rise to the Gutenberg press and the 1918 flu pandemic led to modern vaccine technology. 以黑死病为例,它促成了古腾堡活字印刷术, 还有 1918 年的流感大流行,
The COVID-19 pandemic has and will be no different. 新冠肺炎疫情也不会是例外。
Just look at our vaccines -- normally developed over many years, and the mRNA vaccines were deployed in a mind-blowing 11 months. 看看我们的疫苗就知道—— 通常需要多年的研发, 这次 mRNA 疫苗到部署出来,
Black Death:n.黑死病(14世纪蔓延于欧亚的鼠疫); vaccine:n.疫苗;牛痘苗;adj.疫苗的;牛痘的; vaccines:n.[药][计]疫苗; normally:adv.正常地;通常地,一般地; deployed:v.部署(deploy的过去式);展开; mind-blowing:adj.使兴奋的;引起幻觉的;
How is that even possible? 怎麽可能办到？
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. 能办到,是因为科学家 已经投入多年的努力, 让我们已经能做到快速将 mRNA 用在紧急情况中。
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. 明确来説, 我们一直在研究如何解决 mRNA 最大的问题, 也就是:它一般不会抵达 我们体内正确的目的地。
emergency:n.紧急情况;突发事件;非常时刻;adj.紧急的;备用的; Specifically:adv.特别地;明确地;
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. 幸运的是,我们即时 避开了这个问题。 我想跟各位分享我们用在此的技术。
When mRNA is administered , it's injected into our muscles or our bloodstream , but we actually need it to go inside of our cells. 给予 mRNA 时, 会把它注射到我们的肌肉或血液中, 但我们其实需要 让它进入我们的细胞中。
Unfortunately , mRNA is fragile , and our bodies will destroy it before it goes very far. 不幸的是,mRNA 很脆弱, 走不了多远就会被我们的身体消灭。
Fortunately:adv.幸运地; administered:v.管理;治理(国家);执行;给予;提供;(administer的过去分词和过去式) injected:v.(给…)注射(药物等); (inject的过去分词和过去式) muscles:n.肌肉(muscle的复数); bloodstream:n.[生理]血流,血液的流动; Unfortunately:adv.不幸地; fragile:adj.脆的;易碎的;
You can think of mRNA like a glass vase that you'd like to send in the mail without a box and bubble wrap . 可以把 mRNA 想成玻璃花瓶, 却没有盒子也没有气泡布。
It'll break long before it's been delivered. 远在送达之前,它早已被打破了。
And without an address on the box, your postal delivery service will have no idea where to take it. 而且没有盒子上的地址, 邮政服务也不会知道 该把它送到哪里去。
And so if we're going to use mRNA as a therapeutic , it needs our help. 所以,如果我们要把 mRNA 用在治疗上, 它就需要我们的协助。
bubble wrap:n.气泡膜包装;泡塑包装;气泡垫; postal:adj.邮政的;邮局的;n.明信片; delivery:n.[贸易]交付;分娩;递送; therapeutic:adj.治疗的;治疗学的;有益于健康的;n.治疗剂;治疗学家;
It needs protection, and it needs to be told where to go. 需要保护它,
And that's where I come in. 此时就该我出场了。
For over five decades, scientists and engineers like myself have been creating the shipping materials for nucleic acid drugs, like DNA and RNA. 五十年来, 一直在为核酸药物 创造运送用的包装材料, 比如 DNA 和 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. 透过试误法, 可以把花瓶完好地送达错误的地址。 也可以送到对的地址,但花瓶会破。 也有些包裹会被恶犬咬烂, 也有些包裹会从邮差的背包掉出来。
nucleic acid:n.核酸; intact:adj.完整的;原封不动的;未受损伤的; throw out:v.扔掉;伸出;说出;否决;突出;
It's taken many years to get the science right. 花了非常多年, 才把科学的部分做对。
Let me show you the result, these tiny balls of fat that we call lipid nanoparticles . 让我给各位看看结果, 这些小小的脂肪球,
Let me tell you what they are and how they work. 让我来告诉各位它们是什么,
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. 想想和地球的直径相比, 一个人有多渺小。
That's how small a nanoparticle is compared to the person. 和一个人相比时, 奈米粒子也是那么渺小。[03:24]
lipid:n.[生化]脂质;油脂; nanoparticles:n.纳米粒子(nanoparticle的复数形式); first of all:adv.首先; compared:adj.比较的,对照的; v.相比; (compare的过去式和过去分词) diameter:n.直径;对径;放大率;放大倍数;
These nanoparticles are made up of several fatty molecules called lipids . 这些奈米粒子是由许多叫做 「脂质」的脂肪分子组成。
Fat is an awesome packing material -- nice and bouncy . 脂肪是很棒的包材—— 很好,很有弹性。
Interestingly , our cells are also surrounded by fat to keep them flexible and protected. 有趣的是,我们的细胞 也是被脂肪包围, 让细胞具有弹性且受到保护。
Years ago, scientists had the idea to create lipid nanoparticles that would act like a Trojan horse . 数年前,科学家想出一个点子, 来当作特洛依木马。
made up of:由…组成,由…构成; fatty:adj.脂肪的;肥胖的;多脂肪的;脂肪过多的;n.胖子; molecules:n.[化学]分子,微粒;[化学]摩尔(molecule的复数); lipids:n.脂肪,油脂;[生化]脂类(lipid的复数); awesome:adj.令人敬畏的;使人畏惧的;可怕的;极好的; bouncy:adj.有弹性的;快活的;精神饱满的;自大的; Interestingly:adv.有趣地; flexible:adj.灵活的;柔韧的;易弯曲的; Trojan horse:n.特洛伊木马;(来自外部的)颠覆分子(或活动);
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. 因为奈米粒子中的脂质看起来很像 包围我们细胞的膜, 因此细胞愿意让奈米粒子进入, 此时就可以把 mRNA 释放到细胞中。
So what, exactly, are the lipids in these nanoparticles? 所以,这些奈米粒子中的 脂质到底是什么？
There are four ingredients in addition to the mRNA, and I'll tell you about each one. 除了 mRNA 之外,还有四种成份, 我会一个一个来谈。
First, there's a lipid called a phospholipid . 首先,有一种脂质叫做磷脂。
membranes:n.细胞膜(membrane的复数);薄膜;膜皮; released:v.释放;使免除;已发布;(release的过去分词和过去式) ingredients:n.成分;(尤指烹饪)原料;(成功的)要素;(ingredient的复数) in addition to:除…之外; phospholipid:n.[生化]磷脂;
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. 它是细胞膜的主要成份, 细胞膜是种脂肪墙,把细胞的内部 和周围的一切分隔开来。
Phospholipids have a head that likes water and a tail that likes other fatty things. 磷脂的头部喜欢水, 尾部则喜欢其他有脂肪的东西。
So when you throw a bunch of phospholipids together in water, they form this beautiful structure called a lipid bilayer . 所以,当你把一堆磷脂 一起丢到水中, 就会形式这种美丽的结构,
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. 在这里,头部会面向 细胞的内部和外部, 也就是水, 而分子中喜欢脂肪的部分,就一起待在中间。
Phospholipids:n.[化]磷脂;(phospholipids是phospholipid的复数); a bunch of:一群;一束;一堆; structure:n.结构;构造;建筑物;vt.组织;构成;建造; bilayer:n.双分子层(膜);
In lipid nanoparticles, phospholipids have a similar role of keeping all of the other ingredients organized . 在脂质奈米粒子中, 磷脂也扮演类似的角色, 让所有其他成份能保持井然有序。
Second, there's a lipid called cholesterol . 再来,有一种脂质叫做胆固醇。
Why, if cholesterol has a bad reputation, would we want to use it in a therapeutic nanoparticle? 如果胆固醇的名声这么不好,为什么 我们要把它用在 治疗性的奈米粒子中？
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. 结果发现,虽然血液中 有胆固醇时会很不好, 它其实对我们的细胞膜相当好。
organized:adj.有组织的; v.组织; (organize的过去分词和过去式) cholesterol:n.[生化]胆固醇;
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. 因为,我刚才谈到的磷脂, 它们自己会太过自由, 它们很容易就会散开。
Cholesterol is a stiff molecule that wedges itself in between the other lipids to fill in the gaps and hold them all together. 胆固醇是种很硬的分子, 会把它自己卡在其他脂质之间, 补满空隙,让它们能结合在一起。
It plays a similar role in our lipid nanoparticles. 它在我们的脂质奈米粒子中 也扮演类似的角色。
prone:adj.俯卧的;有…倾向的,易于…的; stiff:adj.呆板的; v.僵硬地; n.死尸; v.诈骗; wedges:n.楔形; v.楔入; gaps:n.差异,缺口;缝隙(gap的复数形式);v.裂开;使豁裂(gap的第三人称单数形式);
It provides structural support so the nanoparticles don't fall apart in between the injection and when they get into our cells. 它能提供结构性的支撑, 进入我们的细胞之前,都不会散开。
Third, there's a lipid called an ionizable lipid. 第三,有一种脂质叫做离子化脂质。
Here, "ionizable" means that when these particles are in the bloodstream, they're neutrally charged, which helps with their safety. 在这里,「离子化」的意思是 属于电中性,这对它们的安全性有幫助。
structural:adj.结构的;建筑的; fall apart:崩溃;土崩瓦解;破碎; injection:n.注射;大量资金的投入;(液体的)注入; neutrally:adv.中立;保持中立;
Then they switch to a positive charge inside of our cells, which helps them release the mRNA. 接着,在我们的细胞中, 它们会换成带正电, 这样能协助它们释放 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. 离子化脂质的特别之处在于 而世界各地的科学家 已经测试过数万种这类材料, 来找出有哪些能够 安全地递送 mRNA。
positive:adj.积极的;[数]正的,[医][化学]阳性的;确定的;n.正数;[摄]正片;
And because they're made in the lab, they tend to be proprietary to the company that invented them. 因为它们是由实验室制造, 它们的所有权通常属于 发明它们的公司。
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. 所以,比如,莫德纳及 BNT,也就是和辉瑞合作的公司。 它们发现了不同的离子化脂质, 它们的新冠肺炎疫苗中就只有这个重要成份是不同的。
proprietary:n.所有权;所有人;adj.所有的;专利的;私人拥有的;
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. 且,尽管如此,它们的离子化脂质也没有非常不同, 这很令人宽慰,因为当独立的科学家团队 得出的解决方案会趋向类似, 就比较容易信赖这个结果。
Finally , one more ingredient. 最后,还有一种成份。
This one is a polymer called polyethylene glycol . 它是一种聚合物,叫做聚乙二醇。
So let's call it PEG . That's much easier. 咱们就称它为 PEG,比较简单。
PEG is a water-loving molecule. PEG 是一种很喜欢水的分子。[07:25]
reassuring:adj.安心的;可靠的;鼓气的;v.使放心(reassure的现在分词); independent:adj.独立的; n.无党派议员(或候选人等); converge:vt.使汇聚;vi.聚集;靠拢;收敛; Finally:adv.终于;最终;(用于列举)最后;彻底地; polymer:n.[高分子]聚合物; polyethylene:n.[高分子]聚乙烯; glycol:n.乙二醇;甘醇;二羟基醇; PEG:n.楔子; v.用夹子夹住; water-loving:亲水的;
So it surrounds the lipid nanoparticle and it holds it all together. 所以它会围绕着脂质奈米粒子,
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. 你可以把另外三种脂质想成是mRNA 的盒子和气泡布, PEG 就是打包用的胶带。
You may have heard in the news about a tiny fraction of people that have allergic responses to the vaccine. 你可能在新闻上看过, 有很低比例的人 对疫苗会有过敏反应。
There is some evidence that PEG could be contributing to these allergic reactions . 有一些证据显示,PEG 可能会促成
And that's because people are routinely exposed to PEG in cosmetic and household products, and some people have already developed antibodies against PEG. 那是因为人会例行性地 接触到 PEG, 在化妆品和家用产品中都有, 有些人已经发展出 对抗 PEG 的抗体。
fraction:n.分数;小部分;小数;少量; allergic:adj.对…过敏的;对…极讨厌的; responses:n.回答,答复;反应;响应;(response的复数) evidence:n.证据,证明;迹象;明显;v.证明; contributing:v.捐献,捐赠(尤指款或物);捐助;增加;增进;(contribute的现在分词) reactions:n.反应;回应;抗拒;生理反应;副作用(reaction的复数) routinely:adv.例行公事地;老一套地; exposed:adj.无遮蔽的; v.暴露; (expose的过去分词和过去式) cosmetic:adj.美容的;化妆用的;n.化妆品;装饰品; household:n.家庭;一家人;同住一所(或一套)房子的人;adj.家庭的;家常的;王室的; antibodies:n.[免疫]抗体(antibody的复数);
But why would this happen to some people and not to others? 但为什么有些人会过敏, 有些人就不会？
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. 结果发现,每个人的 免疫系统都不一样, 和有些人对乳类过敏同样的道理, 也有人会对 PEG 过敏。
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. 不过,很重要的是要记住, 安全使用 PEG 的历史已久, 它是 FDA 核准的 药品配方的一部分。 而这些疫苗过敏也有可能是 PEG 以外的东西所引起。
immune system:n.免疫系统; latex:n.乳胶;乳液; keep in mind:记住; formulations:构想,规划;[数]公式化;简洁陈述formulation的复数); allergies:n.变态反应;过敏反应;(allergy的复数)
More research is needed to get to the bottom of these side effects. 还需要做更多研究才能 弄清楚这些副作用。
All right, so let's take a step back and look at our whole nanoparticle. 好,咱们现在退一步,
Beautiful, right? 很美,对吧？
When these ingredients all fit together nicely , the result is a deliverywoman's dream. 当这些成份通通都完美结合, 结果就是让一位 送货女子的梦想成真。
In the case of the vaccines, after these nanoparticles get injected into our muscle, they take the mRNA into our cells. 就疫苗来说, 奈米粒子被注射进我们的肌肉之后, 它们会把 mRNA 带到我们的细胞里。
There, the mRNA acts like an instruction manual that tells our cells to make a foreign protein , in this case, the coronavirus spike protein. 在那里,mRNA 扮演说明书的角色, 叫我们的细胞去制造 一种外来蛋白质, 在这个例子中, 就是冠状病毒棘蛋白。
nicely:adv.细致地;有吸引力;令人满意;令人愉快;adj.强健的; manual:n.说明书;指南;使用手册;adj.用手的;手工的;体力的;手动的; protein:n.蛋白质; coronavirus:n.冠状病毒;日冕形病毒; spike:n.长钉,道钉;钉鞋;细高跟;vt.阻止;以大钉钉牢;用尖物刺穿;
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. 当我们的免疫细胞看到了棘蛋白, 它们会赶来保护我们,对抗棘蛋白, 它们也会教自己记住这种棘蛋白, 当它再次出现时,它们就能杀了它。
As we speak, the mRNA vaccines are out there saving lives from the coronavirus. 此时此刻, mRNA 疫苗正在外头
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. 它们是我们对抗这场恶梦的 第一个武器,最好的武器, 它们也是我们快速因应 病毒变种的最佳希望, 因为我们可以继续使用 相同的脂质奈米粒子包裹, 我们只要换掉里面的 mRNA 即可。
But here's the best part: for mRNA therapeutics , these vaccines are only the beginning. 但,最棒的是: 就 mRNA 疗法来说, 这些疫苗只是开端。
mRNA can be used to treat or cure many diseases . mRNA 可以用来治疗 或治愈许多疾病。
So in the future, we will likely have treatments for many terrible diseases, including cystic fibrosis , muscular dystrophy and sickle cell anemia . 所以,在未来,我们可能可以治疗许多可怕的疾病, 包括囊肿性纤维化、 肌肉萎缩症, 以及镰刀型红血球疾病。
combat:v.战斗;防止;减轻;与…搏斗;n.战斗;搏斗;打仗; nightmare:n.恶梦;梦魇般的经历;adj.可怕的;噩梦似的; responding:v.响应;作出反应;反应灵敏;(respond的现在分词) swiftly:adv.很快地;敏捷地;即刻; viral:adj.滤过性毒菌引起的;滤过性毒菌的; variance:n.变异;变化;不一致;分歧;[数]方差; swap:n.交换;交换之物;vt.与...交换;以...作交换;vi.交换;交易; therapeutics:n.疗法,治疗学; treat:v.治疗;处理;招待;款待;n.款待;乐事;乐趣; diseases:n.[医]病(disease的复数);[医]疾病;[植保]病害;疾病种类; treatments:n.治疗;疗法;对待;处理;讨论;(treatment的复数) cystic fibrosis:n.囊性纤维化; muscular dystrophy:n.肌营养不良症;肌肉萎缩; sickle:n.镰刀; anemia:n.贫血;贫血症;
These diseases are caused by mutated proteins , and we can use mRNA to ask our cells to make the correct version of these proteins. 造成这些疾病的是突变的蛋白质, 而我们可以用 mRNA 来要求我们的细胞 制造出这些蛋白质的正确版本。
We'll have treatments for cancer -- breast, blood, lungs -- you name it. 我们将来也能治疗癌症——乳癌、血癌、肺癌—— 想得到的都行。
Here, we'll use mRNA to teach our immune cells how to find and kill cancer cells. 在这个应用上, 如何找到并杀死癌细胞。
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 . 接着,够幸运的话, 对抗全球各地一些最致命、最让人惧怕的病原体, 包括疟疾、伊波拉, 以及人体免疫缺损病毒。
mutated:突变;变成;经受突变; proteins:n.[生化]蛋白质(protein复数); cancer:n.癌症;恶性肿瘤; deadly:adj.致命的;非常的;死一般的;adv.非常;如死一般地; pathogens:n.[基医]病原体;病原菌;[基医]致病菌; malaria:n.[内科]疟疾;瘴气; Ebola:n.埃博拉病毒; HIV:n.艾滋病病毒;
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 . 这些产品当中已经有部分 在进行临床试验了, 而新冠肺炎疫苗的成功, 也是为未来世代, 幫这些治疗方式铺路。
This is how the pandemic will save the lives of millions. 这就是疫情拯救 数百万人性命的方式。
It catalyzed the most rapid vaccine development in history and brought to life a niche , previously unapproved form of technology. 它催化了史上最快速的疫苗开发, 催生了一个利基,先前未被承认的技术形式。
clinical:adj.临床的;诊所的; pave the way for:为铺平道路;为…创造条件; therapies:n.治疗方法(therapy复数形式); catalyzed:催化; niche:n.壁龛; vt.放入壁龛; previously:adv.先前;以前; unapproved:adj.未经批准的;未经同意的;未经承认的;
And in our desperation, we gave that technology a chance. 在绝望之际,我们给了那项技术一个机会。
Now we're collecting long-term safety and efficacy data from hundreds of millions of people. 现在我们在收集长期的 安全性和效力资料, 来自数亿人的资料。
And with these data, interest in the technology, funding for the technology and trust in the technology will continue to grow. 有了这些资料, 给这项技术的资助, 以及对这项技术的信任, 都会持续增长。
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. 至于将来, 包装并递送mRNA 给正确的器官及组织, 仍然会是导入这项技术的 重大挑战之一。
long-term:adj.长期的;从长远来看; efficacy:n.功效,效力; funding:n.基金;资金;提供资金;v.为…提供资金;拨款给;(fund的现在分词) organs:n.[生物]器官;机构;风琴(organ的复数); tissues:n.纸巾,手巾纸;(人、动植物细胞的)组织;(tissue的复数) significant:adj.重大的;有效的;有意义的;值得注意的;意味深长的;n.象征;有意义的事物; implementing:n.实施,执行;实现;v.贯彻,执行(implement的现在分词);
And so my colleagues and I are going to be busy for a very long time. 所以我和我同事将会 忙碌很长的一段时间。
Ultimately , I'm here with a message of hope. 最终,我是要带给大家 一个希望的讯息。
We are on the cusp of a revolution . 我们正在革命的关口上。
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. mRNA 将要永远改变世界, 全都要感谢这些小小的脂肪球, 将这种奇迹之药带到需要它的地方。
colleagues:n.同事;同行(colleague的复数); Ultimately:adv.最终;最后;归根结底;终究; cusp:n.尖头;尖端; revolution:n.革命;旋转;运行;循环; is about to:眼看就要;即将;正要;行将; miracle:n.奇迹,奇迹般的人或物;惊人的事例;
Thank you. 谢谢。
(Applause) （掌声）