未登录,请登录后再发表信息
最新评论 (0)
播放视频

其实新冠mRNA疫苗的制造花了50年

Why It Actually Took 50 Years to Make COVID mRNA Vaccines

[♩INTRO]
[♩导入曲]
When the COVID-19 pandemic began,
新冠疫情开始的时候
researchers and public health experts warned us
研究人员和公共卫生专家发出警示
that the earliest possible window for a vaccine would be the end of 2020.
说疫苗最早要到2020年底才可能做出来
They also cautioned us that vaccine development takes time,
他们又说 研发疫苗需要很长时间
and it could be much longer than that.
也可能会远远超过2020年底
But in the closing weeks of the year, two vaccines
结果就在那年最后几周 两支疫苗
one from pharma companies Pfizer and BioNTech, one from Moderna
一支来自医药公司辉瑞和BioNTech 另一支来自莫德纳公司
began rolling out in some parts of the world.
开始在世界上一些地区投入使用
They weren’t the first worldwide,
它们虽不是全球第一种新冠疫苗
but they were, in a sense, the first of their kind.
却可以说是同类型中最早的疫苗
And like Babe Ruth calling his shot,
那些专家就像神算子一样
it seems a little like the experts knew how this was going to go.
他们似乎预见了疫情的爆发
And that’s because a technology decades in the making
其实是有一种科技已经酝酿了几十年
was finally able to rise to the occasion — just when we needed it most.
终于在我们最需要它时出现了 解了我们的燃眉之急
This is the story of how a new vaccine technology, based on RNA, came to be.
这是个新型RNA疫苗技术诞生的故事
And if it continues to prove safe and effective,
只要安全性和有效性持续得到保证
it won’t just be for COVID.
不只是新冠疫苗
It will be a major change in the way we design all vaccines in the future.
未来所有疫苗的研发过程都将发生变革
Now, we’re going to cover a lot of research today
今天我们会提到很多很多研究
but none of these papers were published out of the blue.
这些研究论文的发表并非出于偶然
A lot of progress in immunology and biotech had to happen
在免疫学和生物科技都有了巨大进步的前提下
for mRNA vaccines to happen,
mRNA疫苗才应运而生
and a lot of people had to do that research.
而且这是很多人辛勤钻研的结果
The job of a vaccine is to safely expose our immune system to an antigen—
疫苗让我们的免疫系统安全地暴露给抗原
a piece of protein from a pathogen, or infectious agent,
抗原是病原体的一部分蛋白质
that our immune system will remember and recognize.
免疫系统将会记住并识别它
It’s like a wanted poster
疫苗就像一张通缉令
that will teach our immune cells what to seek out and destroy
让免疫细胞能够在真的发生病毒感染时
when a real infection happens.
找到病毒并消灭掉
Traditionally, we’ve introduced antigens in a few different ways:
现在说一说几种引入抗原的传统方式:
using a live weakened pathogen (so one that is alive but won’t hurt us),
用减毒病原体(有活性但不会伤害人体)
a killed pathogen, or just a piece of one.
灭活病原体 或者是病原体的一部分
We’ve also used viruses to deliver instructions to our cells to make an antigen.
或让病毒去给细胞下达制造抗原的指令
Whatever method you use, this takes years of work.
不管用上述哪种方式都需要很多年
For example, to make the measles vaccine,
举个例子 为了做麻疹疫苗
scientists had to grow the virus for almost ten years.
科学家花了近十年培育病毒
They needed to weaken the virus enough
他们得让病毒足够弱
that it would trigger an immune response without making you sick.
弱到恰好能激发免疫反应 又不会致病
But starting around the 1990s,
然而到了20世纪90年代
scientists thought that maybe they could cut out the middleman
科学家觉得或许可以跳过中介
and use messenger RNA, or mRNA, to reprogram our cells
直接用信使RNA 也就是mRNA 来重编程细胞
so they make those viral antigens by themselves.
使它们自身可以直接制造病毒抗原
Instead of us producing them in a laboratory somewhere,
这样就不用在实验室里人工制造抗原了
our cells could do the work.
我们的细胞自己就能制造
They hoped that such an approach might be safer and more efficient than traditional vaccines,
他们希望这种疫苗至少对某些疾病来说
at least for some diseases.
比传统疫苗更安全有效
After all, the job of RNA is to guide the production of proteins in a cell,
毕竟RNA的工作就是在细胞内指导蛋白质生产
and antigens are generally proteins.
而且抗原基本上都是蛋白质
But mRNA isn’t actually the genetic material inside our cells – that’s DNA.
然而mRNA并不是我们体内的遗传物质 DNA才是
You can think of DNA as a giant library containing the blueprints
DNA就像一个藏有图纸的巨型图书馆
for any kind of protein your body might need to make.
人体参考图纸制造任何所需的蛋白质
But, since it doesn’t make sense to schlep the whole library with you
不过呢 每次需要“人体加工厂”制造某物时
every time you need to ask a manufacturing plant to make something,
都把整个图书馆拖过来有点说不过去
it’s easier to just copy out the specific protein blueprints you want.
简便做法是把你要的那份蛋白质图纸拷贝出来
mRNA is that copy.
mRNA就是这份拷贝
It brings the genetic sequence for a protein
它会把蛋白质的基因序列
transcribed from a cell’s DNA to the place where proteins are made.
从某个细胞的DNA转录过来 带到生产蛋白质处
mRNA vaccines use this feature
mRNA疫苗利用了这个特点
to safely coax our cells
成功诱使细胞
into using their own protein-making machinery
用自己的蛋白质制造系统
to create a viral antigen — from scratch.
从无到有创造病毒抗原
And this turns out to be a big advantage
当你需要解决某些问题
when you’re dealing with something
例如一种引起了突发疫情的全新病毒时
like a totally new virus causing a sudden pandemic.
这就成了mRNA疫苗的巨大优势
Because designing one of these vaccines doesn’t even require a sample of the virus —
因为研发这种疫苗连病毒样本都不需要
all you need is a digital file with its genetic sequence.
只要病毒基因序列的数字文件就够了
That’s because as long as you know the sequence of DNA or RNA,
因为只要知道DNA或RNA的序列
you can just make it.
你就能制造mRNA疫苗
It is not nearly that simple with protein-based antigens.
而制造蛋白基抗原就没那么容易了
Proteins are all foldy and weird.
蛋白质卷曲折叠 奇形怪状
DNA and RNA are just linear strings.
而DNA和RNA只是线性的链
Scientists can simply download the genetic sequence of the virus
科学家只需要下载病毒的基因序列
and have a candidate vaccine ready to start testing within weeks or even days.
在数周甚至几天里 就能做好候选疫苗并开始测试
That’s what happened with Moderna’s vaccine,
这也是为什么莫德纳的疫苗
which was ready for preliminary tests less than a month
在新冠病毒的基因组被发到网上以后
after the genome of the SARS-CoV-2 virus was published online.
不到一个月就开始了初步测试
Also, this enables a plug-and-play approach.
同时 这种方法是“即插即用”的
Once you have all the basic pieces to make an mRNA vaccine in place,
一旦准备好了制作mRNA疫苗的所有东西
you don’t need a new setup to make a new vaccine for a new virus.
在针对新病毒制作疫苗时 你不需要重新设置
Theoretically, you can just swap in new RNA and go from there.
理论上只需要换入新的RNA就能开始接下来的工作
And there’s also one more reason they’re so speedy to put together.
除此之外 开发速度这么快还有一个原因
Many vaccines require adjuvants.
许多疫苗都需要佐剂
These are substances that enhance the immune system’s response to the vaccine
这些佐剂会增强免疫系统对疫苗的反应
and attract the right immune cells.
并吸引正确的免疫细胞
But mRNA, it turns out,
但是mRNA不用佐剂
is pretty good at bringing in the immune system all by itself.
它本身就很擅长激发免疫系统
So it avoids the potential need to spend additional months or years
也就避免了另外再花几个月或几年
testing various types and amounts of adjuvants,
来测试各种类型和剂量的佐剂
and whether they’re necessary to make the vaccine work.
以得知它们是否能让疫苗起效
You can see how all of this could make mRNA vaccines the perfect technology
综上所述 当我们需要迅速应对一种新型流行病时
to rely on when we need a defense against a new pandemic, stat.
mRNA疫苗技术是我们的完美依靠
But there’s a reason why we’re only now hearing about them.
但为什么我们到现在才听说mRNA疫苗呢
Because they just weren’t ready before.
因为之前科技还不完备
You see, for all of its benefits, mRNA also has some drawbacks,
尽管优势明显 mRNA也有缺陷
which have taken literal decades of research to resolve –
为了攻克它 科学家足足研究了几十年
just in time for COVID-19.
新冠爆发时才恰好成功
This research got its start around 1971,
这项研究1971年左右就开始了
when UK-based researchers studying protein production
那时 研究蛋白质生产的英国科学家
put mRNA from a rabbit into frog egg cells.
把兔子体内的mRNA注入青蛙卵细胞中
They found that those cells produced the rabbit version of that protein,
他们发现青蛙细胞制造出了兔类的蛋白质
thanks to the mRNA code.
靠的就是mRNA编码
This led to a series of similar experiments, with scientists being able
科学家又做了一系列类似的实验
to insert mRNA into more and more complex types of cells.
他们把mRNA注入越来越复杂的细胞内
Researchers also kept working on efficient ways to deliver mRNA into a cell.
同时研究注入的有效途径
The first experiments in using mRNA as an actual vaccine
真正把mRNA用作疫苗的实验
started taking place in the early 1990s.
最早始于20世纪90年代早期
And that is where researchers ran into huge problems.
也就是那时候 科学家遇到了难题
The major roadblock was that when it’s introduced into the body,
主要的障碍是 当疫苗被注入体内后
RNA can be pretty hard to keep in one piece.
RNA几乎很难保持完整
It turns out that free-floating RNA is often used by tumor cells
原来 肿瘤细胞常会利用自由移动的RNA
to make it easier for them to spread around.
让自身的扩散变得更容易
RNA that hangs around outside of our cells can also
另外 散落在细胞外的RNA也可能是
be a remnant of a cell that was infected by a virus and then blasted apart by the immune system.
某细胞因感染病毒被免疫系统瓦解后形成的碎片
And so, to keep us healthy from those two things,
为避免这两者危害健康
our bodies have a lot of ribonucleases,
人体内有很多核糖核酸酶
which are enzymes that break up free-floating RNA
这些酶会破坏自由移动的RNA
to get rid of any potential danger.
来避免潜在危机
So that’s why in early experiments,
于是乎在早期实验中
mRNA would get destroyed before enough of it
mRNA在进入细胞前就遭到破坏
could get into a cell and start doing its magic.
导致数量不足 无法发挥奇效
This problem stymied mRNA vaccine research for decades,
这个问题阻碍了近几十年的疫苗研究
until scientists found ways to make the mRNA more stable.
直到有科学家找到让mRNA更稳定的方法
One solution was adding specific gene sequences
一种办法是添加某种特定的基因序列
to cap the beginning and the end of the mRNA strand.
给mRNA链的前端和末端加帽
That made it look more like mRNA that was generated by our own body.
让它看起来更像人体自身产生的mRNA
But that wasn’t the only quirk of messenger RNA that scientists had to contend with.
然而这不是mRNA带给科学家的唯一难题
On top of the ribonuclease problem,
除了核糖核酸酶的问题
free-floating RNA can activate the immune system
自由移动的RNA还会激活免疫系统
and attract it to its location.
并把免疫细胞引过来
Yeah, sure, like we said before, attracting the immune system can be helpful,
当然 如前述 激活免疫系统有益处
because you need that to happen for a vaccine to work anyway.
因为那样疫苗才能发挥作用
But this was too much of a good thing.
不过物极必反
In early attempts, the mRNA was activating the immune system so much
早期实验中 免疫系统被mRNA过度激活
that it would clear the vaccine away before it could do its job.
疫苗发挥作用之前就被免疫系统清除了
Like, the goal of using an mRNA vaccine
用mRNA疫苗的目的
is to teach the immune system to seek out the antigens
是教会免疫系统找出要制造的抗原
that the vaccine will program our cells to make.
并给细胞编程 来制造这些抗原
Not to destroy the message before it gets the chance to do anything.
而不是在此之前就让“生产图纸”被毁
And then we reached 2005 when researchers discovered
终于在2005年 研究人员发现了
the secret handshake that allows our bodies’ RNA to avoid immune destruction.
人体内RNA没被免疫系统销毁的原因
You see, RNA is composed of four chemical bases,
我们知道 RNA由四种碱基组成
which mirror those used in DNA.
与DNA的碱基一一对应
But it turns out that in mammals, a lot of those bases are chemically modified
然而哺乳动物的许多碱基经过化学修饰
until the mRNA strand is needed to guide the creation of a protein.
直到需要mRNA链来指导蛋白质合成
This is not the case in most pathogens.
这跟多数病原体不太一样
That’s why when the immune system notices a strand of unmodified RNA,
于是当免疫系统发现未经修饰的RNA时
it’s a clear sign that it’s dealing with an invader
就会把它明确识别为入侵者
and then, it’s time to mount an attack.
然后发动攻击
Figuring this out meant that scientists could now apply
这个发现意味着科学家可以
those chemical modifications to manufactured RNA.
对生产出的RNA进行化学修饰
In fact, it actually made mRNA vaccine technology more customizable.
其实 这使mRNA疫苗更加可定制化
Basically, researchers could tweak the percentage of modified bases
只要科学家稍稍调整修饰碱基的比例
in the mRNA just enough to call the immune system to the area
就能使mRNA恰好激活免疫系统
but not enough to induce an all-out attack
又不会诱发其对RNA的毁灭性攻击
and deactivate the vaccine before it can start helping your body.
也不会让疫苗开始发挥作用前就失效
Alright, we have done a lot of work here,
从20世纪70年代到21世纪初
from the 1970s to the early 2000s.
我们解决了不少事情
The final challenge that scientists had to overcome
科学家面临的最终挑战是
was how to deliver the vaccine into the cell.
如何把疫苗输送到细胞中
The mRNA molecule itself is too big to get through a cell’s membrane easily.
mRNA分子太大 很难自己穿过细胞膜
Experiments demonstrated that some can sneak in,
实验显示有一部分可以溜进去
but not enough that you could just throw it at cells and hope for the best.
但太少了 不足以寄希望于它们能干什么
Now, there are specialized ways
现在有专门的方法
to introduce nucleic acids into cells in a lab setting.
在实验室环境下把核酸导入细胞中
But they aren’t always suitable for use in a living human body.
然而这些办法在活的人体中并不太合适
Things like zapping the cells with electricity to open little holes to let things in.
比如有的办法是通过电击细胞开个小洞让东西进去
It’s not that these methods can’t be adapted for use in humans,
不是说这些方法完全无法适用于人体
it’s just that there are better options than zapping people.
只不过还有比给人打洞更好的选择
A simple injection is what we want —
我们只想简单地打一针
something people are used to,
一是大家习惯注射疫苗
also something we have all of the technology already to administer,
二是如果你要给几十亿人口安全快速地接种
especially if you want to fairly quickly vaccinate billions of people.
最好用那些成熟到随时可投入使用的技术
And that’s why scientists eventually turned to lipid nanoparticles,
这就是为何科学家最后采用了脂质纳米粒
which are the delivery method used
这种传递方法
in the first two mRNA vaccines to hit the market.
正是头两支投放市场的疫苗所采用的
Lipid nanoparticles, or LNPs, are tiny balls of layered lipids, or fats,
脂质纳米粒 也叫LNP 是层状的脂质或脂肪小球
with an mRNA payload tucked safely inside.
内部载有足量mRNA
The LNPs have a positive charge,
LNP带有正电荷
which makes them stick to the negatively charged cell membranes.
会吸附在有负电荷的细胞膜上
In a process called endocytosis,
在一种叫“内吞作用”的过程中
the cell then wraps the LNP in a piece of its membrane
细胞用一部分细胞膜包裹住LNP
and swallows the package.
并吞下“包裹”
Once inside, our cellular machinery unpacks the whole package,
细胞的机制使“包裹”被打开
and the mRNA can start making the antigen proteins necessary
这时mRNA开始制造必要的抗原蛋白
to train our immune system.
来训练我们的免疫系统
And this isn’t that new of a technology.
这项技术并不新鲜
As early as 1978, scientists were able to use a basic version of these tiny balls of fat
早在1978年 科学家就用基本版小脂球
to get the mRNA inside mouse spleen cells
让mRNA成功进入老鼠的脾细胞
and make them synthesize a new protein.
促使脾细胞合成一种新的蛋白质
Early LNPs had some issues with efficacy,
早期LNP的效果不够好
but researchers eventually perfected the technology,
不过研究人员最终完善了科技
just a few years before it turned out to be needed
只过了几年 这项技术就派上了用场
to quickly develop an mRNA vaccine for the COVID-19 pandemic.
让我们快速制造出了应对新冠疫情的mRNA疫苗
Building on successful studies in delivering other types of RNA into cells,
因为有让其他种类的RNA进入细胞的成功案例
in the early 2010s, researchers started experimenting with LNPs
21世纪10年代早期 研究人员开始实验
as ways to make mRNA vaccines easily injectible.
用LNP让注射mRNA疫苗变得更简单
And in 2018, the FDA approved
在2018年 FDA批准了
the first RNA drug that also used LNPs.
第一支也使用了LNP的RNA药物
Which means the delivery vehicle was ready just in time
这意味着当研究人员开始为新冠病毒
when researchers started working on mRNA vaccines for COVID-19.
研究mRNA疫苗时 LNP恰好准备就绪
So even though the Pfizer-BioNTech and Moderna COVID-19 vaccines
尽管辉瑞-BioNTech和莫德纳的新冠疫苗
were the first mRNA vaccines to be authorized,
是首批获得批准的mRNA疫苗
researchers had been excited about the potential of this technology
研究人员其实早就看到了这项技术的潜能
and had been working on it for decades.
并为此研究了几十年
It’s true we’ve thrown a lot of money and person-hours at stopping this pandemic,
我们的确为了阻止这场疫情耗费大量人力财力
and without that investment,
倘若没有这些投资
we probably would not be seeing mRNA vaccines just yet.
mRNA疫苗可能还无法面世
Some efforts to create other mRNA vaccines
其他mRNA疫苗也曾被倾注心血
had already been abandoned,
却颗粒无收
and mRNA vaccines were never considered a sure thing.
mRNA疫苗从未被视为一定会实现的事
We had to do the testing, which is why it took until late-2020.
我们不得不反复试验 所以拖到了2020年底才得以成功
But there was an existing body of research to draw from,
不过当时有一些研究实例可供参考
including into other major coronavirus diseases — SARS and MERS.
例如针对其他主要冠状病毒的研究 像SARS和MERS
What researchers learned allowed them to create
科学家已掌握的信息能帮助他们
these new COVID vaccines even faster.
更快地开发出新冠疫苗
In one sense, these COVID vaccines were an explosive development,
某种意义上 这些新冠疫苗借人类健康之名义
an incredibly swift global collaboration in the name of human health.
实现爆发式发展与全球极速联动
Something that feels, to me, on the scale of an Apollo mission.
对我来说 这个规模就像阿波罗号探月任务
But all science is incremental.
不过所有科学都是逐步发展的
It always builds on the dedicated work of generations of researchers.
总是需要数代人的刻苦钻研
And it never happens in a vacuum.
绝不是凭空而来
In fact, multiple mRNA vaccines for other viral and bacterial diseases,
实际上 多种针对其他病毒性或细菌性疾病的mRNA疫苗
and even for some cancers, are undergoing human trials.
甚至针对癌症的疫苗 都进入了人体试验阶段
Now that mRNA vaccines are working,
既然mRNA疫苗已经初见成效
it’s likely they will keep working.
接下来定会发挥更多作用
And that is great news for all of us.
这对我们所有人来说都是好消息
Thanks for watching this episode of SciShow.
感谢观看本集科学秀
We hope it’s helped you understand how we got this far.
希望助你了解了mRNA疫苗的由来
I know that I personally, before I saw this script, didn’t know a lot of this history.
我个人在看讲稿前也不太了解这些研究经过
If you want to help us as we try to make this complicated world
如果你想协助我们把这个复杂的世界
a little easier for everyone to understand, consider supporting us on Patreon.
变得更易于理解 可以在Patreon上支持我们
Patrons get access to cool perks,
赞助人会获得额外福利
like monthly livestreams and bloopers.
比如每月直播和幕后花絮
And we couldn’t do this without your support, so thank you.
我们离不开你们的支持 感谢你们
To get involved, check out patreon.com/scishow.
想支持我们 请访问patreon.com/scishow
[♩OUTRO]
[♩结束曲]

发表评论

译制信息
视频概述

因为新冠疫情,mRNA疫苗走入了我们的视线,但这其实是全球许多科学家五十年刻苦钻研的结果。科技发展从不是凭空而来。

听录译者

收集自网络

翻译译者

云团子

审核员

审核员YY

视频来源

https://www.youtube.com/watch?v=XPeeCyJReZw

相关推荐