Could this technology end all viruses?

翻译人员: Grace Man 校对人员: Shuhui Huang

This round structure is only about ten billionths of a meter in diameter,

这个圆形结构的直径只有 一百亿分之一米，

but it— as well as other technologies in the pipeline—

但是它同其它 正在研究中的科技一道，

could be stepping stones to a monumental public health ambition:

有可能成为人类实现公共卫生领域 里程碑式突破的铺路石：

a single vaccine that protects you against everything.

可以提供一切保护的疫苗。

We’ll get back to the grand vision later, but first,

我们之后会回来讨论这个宏伟蓝图， 但是首先，

let’s start with something that’s being developed now:

我们从一些目前 正在被研发的东西说起：

a vaccine that would protect you against every strain of the flu—

一种可以使你免受 所有流感病毒毒株感染的疫苗——

even ones that don’t exist yet.

甚至是那些 还不存在的毒株。

Here’s one flu virus particle.

这是一个流感病毒粒子。

On the inside is the virus’ RNA,

其内部是该病毒的 核糖核酸 (RNA)，

and on the outside are lots and lots of hemagglutinin proteins.

而外部则有许许多多的

血球凝集素蛋白质 （简称“血凝素”）。

Hemagglutinin attaches to a receptor on a human cell

血凝素附着在人类细胞的受体上，

and fuses the viral and human membranes, starting the infection.

将病毒与人体细胞膜融合， 开始感染过程。

Hemagglutinin is also one of the things your immune system recognizes

血凝素也是你的免疫系统识别最多且 做出最多反应的物质之一。

and reacts to the most.

To understand how this works,

想要理解这是如何运作的，

think of hemagglutinin as a bust of 19th century French Emperor Napoleon Bonaparte.

将血凝素想象成十九世纪法兰西皇帝 拿破仑的半身像。

Croissant!

Croissant! （法语：“可颂面包”的意思。）

If you show Napoleon to an immune system and say, “remember him,”

如果你给免疫系统看拿破仑半身像， 并告诉免疫系统：“记住他，”

the immune system will mostly focus on his head.

拿破仑的头 会是免疫系统关注的重点。

And the same is true for the real hemagglutinin.

对于真正的血凝素来说也是一样。

One way the immune system remembers things

免疫系统记住物质的方法之一是 通过物理上交互接触。

is by physically interacting with them.

Think of it as making plaster molds of parts of the head:

把这个想象成 制作一部分头部的石膏模具：

we call these molds antibodies.

这些模具被称为“抗体”。

The antibodies float around your bloodstream for a while

抗体会随着你的血液流动一段时间，

and then can diminish,

而后会减少，

but blueprints on how to make them are stored in specialized memory cells,

但是制作它们的设计图 已经被特定的记忆细胞储存，

waiting for future Napoleons to invade.

等待着未来的拿破仑们进攻。

Here’s the thing, though.

不过，有一个问题。

Hemagglutinin is constantly mutating.

血凝素是不断变异的。

Most mutations are subtle,

大部分变异非常细微，

produced by single letter changes in the virus’ RNA: like this or this.

由病毒RNA上的单碱基改变造成： 像是这样，或是这样。

Over time, Napoleon-slash-hemagglutinin’s head can change enough

随着时间的推移， 拿破仑头部式样的血凝素

会发生足够多的改变，

that our antibodies become less good at recognizing it.

导致抗体越来越不擅长识别它们。

This is called antigenic drift.

这被称为“抗原漂移”。

Influenza is constantly drifting;

流感就是在不停的漂移当中；

that’s one reason you have to get a new flu shot every year.

这是你需要每年接受 一次新的流感疫苗的原因。

But sometimes bigger changes happen.

但是，有时候会发生更大的变化。

An animal, usually a pig, can get infected with, say,

一种动物，通常是猪， 可以感染上

a human flu and a bird flu.

人类流感和禽流感。

And those different viruses might infect the same cell.

这些不同的病毒 有可能感染相同的细胞。

If that happens, the two different viral genomes can recombine

这种情况一旦发生， 两种不同病毒的基因组就可能

in tens or even hundreds of ways.

以数十种甚至上百种方式重组。

The human flu virus could pick up a bird flu hemagglutinin

人类流感就可以组合 从未感染过人体的禽流感血凝素。

that’s never infected humans before.

This is called antigenic shift,

这被称为“抗原转换”。

and if you get infected by this version of influenza,

如果你一旦感染上这种版本的流感，

none of the antibodies against Napoleon's head are going to help you.

任何“拿破仑头部”抗体 都帮不了你。

Antigenically shifted viruses have the potential

抗原转换而来的病毒 可以迅速感染很多人，

to infect many people very quickly,

causing epidemics and sometimes pandemics.

引发传染病， 甚至是全球性的流行病。

A truly universal flu vaccine would be able to protect

一个真正普遍适用的流感疫苗的 保护范围

against current flu strains and future drifted or shifted strains.

不仅包括当前的流感病毒毒株感染， 也包括未来漂移或转换过的毒株。

But how do we design a vaccine against a strain that doesn’t exist yet?

但是我们如何设计疫苗来 对抗还不存在的毒株？

We look to the past.

我们用历史数据。

There are key parts of hemagglutinin that haven’t changed much over time

血凝素中的一些关键部分 并没有随着时间的推移改变很多，

and are probably critical to infect human cells;

但却可能对入侵人体细胞很重要。

these “conserved regions” could be promising targets for universal vaccines.

这些“保守区域”会是研发 普遍适用疫苗的希望。

But there's a problem that's hindered classical vaccine production.

但是在传统疫苗的生产过程中， 有一个阻碍。

Many conserved regions are in the neck,

很多保守区域都是在颈部，

and it’s tough to get the immune system to react to the neck.

而使免疫系统对颈部做出反应是 十分困难的。

Also, because influenza-like viruses have been around

另外，由于流感类病毒已经 存在数亿年了。

for hundreds of millions of years,

there may not be a single region that’s common across all species

或许已经没有这样一个单独的区域，

存在于流感病毒的 所有种类与亚型里。

and subtypes of influenza.

But there’s promising science in development.

但是仍有充满希望的科学研究 正在进展当中。

Remember this?

记得这个吗？

This is a protein called ferritin;

这个蛋白质叫做“铁蛋白”；

Its normal purpose is to store and move iron.

它的正常功能是 储存以及转移铁离子。

But it’s also the rough size and shape of a small virus.

它的大小和形状与小型病毒相似。

And if you attach viral proteins to it, like this,

如果你将病毒蛋白附着在它上面， 就像这样，

you’d have something that looks, to an immune system, like a virus—

那么对于免疫系统来说， 它看起来就像个病毒——

but would be completely harmless and very engineerable.

但是它完全无害又 容易被设计改造。

Recently, scientists engineered a ferritin nanoparticle

近期，科学家设计出一种 铁蛋白纳米颗粒，

to present 8 identical copies of the neck region of an H1 flu virus.

载有某H1亚型流感病毒颈部区域 八份完全相同的复制体。

They vaccinated mice with the nanoparticle,

他们为老鼠注射纳米颗粒疫苗，

then injected them with a lethal dose of a completely different subtype,

然后给老鼠们注射 致死剂量的H5N1病毒，

这是与H1完全不同的病毒亚型。

H5N1.

All the vaccinated mice lived; all the unvaccinated ones died.

所有注射过疫苗的老鼠都活了下来； 而未注射疫苗的老鼠都死了。

Going one step beyond that,

更进一步，

there may be conserved regions that we could take advantage of

有一些不同但彼此关联的病毒，

across different-but-related virus species—

我们可以对它们之间的 保守区域加以利用。

like SARS-CoV-2, MERS,

例如，2019新型冠状病毒， 中东呼吸综合症冠状病毒，

and a few coronaviruses which cause some common colds.

和一些普通感冒的冠状病毒。

Over the past few decades,

在过去的几十年里，

a different part of the immune system has come into clearer focus.

免疫系统当中的一个不同的部分 已经受到更明确的关注。

Instead of antibodies, this part of the immune system

与抗体不同， 这部分免疫系统

uses a vast array of T cells that kill, for example,

使用大规模T细胞方针去杀死

cells that have been infected by a virus.

那些被病毒感染的细胞。

Vaccines that train this part of the immune system,

在抗体反应的基础上， 如果疫苗可以

in addition to the antibody response, could provide broader protection.

调动训练免疫系统的这一部分， 就能提供更广泛的保护。

A universal flu vaccine would be a monumental achievement in public health.

普遍适用的流感疫苗将会是 公共卫生领域里程碑式的成就。

A fully universal vaccine against all infectious disease is— for the moment—

而可以完全对抗所有传染疾病的疫苗 ——此时此刻——

squarely in the realm of science fiction,

只存在于科幻小说里，

partially because we have no idea how our immune system would react

部分原因是我们无法得知， 如果我们训练免疫系统去

if we tried to train it against hundreds of different diseases at the same time.

同时抵抗数百种不同的疾病， 免疫系统究竟会作何反应。

Probably not well.

结果可能不太好。

But that doesn’t mean it’s impossible.

但这并不意味着 它是完全不可能的。

Look at where medicine is today compared to where it was two centuries ago.

看看与两个世纪前相比， 如今的医学发展已经进步了多少。

Who knows what it’ll look like in another 50 or 100 years—

谁知道再过 50 年或 100 年 它会变成什么样呢——

maybe some future groundbreaking technology

或许会带来真正意义上 普遍适用的疫苗的

will bring truly universal vaccines within our grasp.

未来具有突破性的技术， 已经指日可待。