How to biohack your cells to fight cancer - Greg Foot

翻译人员: Yichen Huang 校对人员: Tianji (Homer) Li

Ok, so you,

好，所以你

are a 4 billion year old meat robot.

是一个四十亿岁的肉身机器人。

Yeah, you heard me right.

对，你没听错。

In fact, as you're made of 30-ish trillion cells,

事实上，因为你由约 30 万亿细胞构成，

and each of those have their own task,

而这些细胞又各司其职，

you're a robot made of trillions of mini robots-

你是一个由数万亿小机器人 构成的大机器人——

you are a mega-meat-bot!

你是一个巨型肉身机器人！

And your mission, for the past 4 billion years or so-

而你的任务， 在过去大概四十亿年——

and for as long as you keep playing this game of life-

直到你离开生命的世界——

is to safeguard the code.

是守护遗传编码。

To duplicate it. To pass it on.

复制遗传编码， 传递遗传编码。

The thing is, you're rubbish at copying your own code.

但问题是，你很不擅长 复制你自己的遗传编码。

Every time it's copied, errors crop up.

每次复制中都可能出现错误。

Not good when an error makes a robot worse at surviving,

错误有时会降低 机器人的生存能力，

but sometimes a mistake helps them survive...

但有时也会让他们更善于生存……

and they pass that glitch in the code on-

他们会传承那些有利的编码——

that's evolution in a nutshell, right?

简而言之，那就是进化，对吧？

Which means you're not the result of some fancy design, I'm afraid.

也就是说， 你恐怕不是什么精妙的设计，

You're a result of billions of years of bad copies.

而是数十亿年不完美复制的产物。

Go you.

真有你的。

Another reason you're not totally awesome

另一个你不完美的理由：

is because that megabot of yours often breaks down.

你巨型机器人的 身体经常会故障。

Fortunately,

cardiologists, immunologists, microbiologists- all the "ists"-

幸运的是，

心脏病学家、免疫学家、 微生物学家——各种“学家”们

have spent centuries figuring out our sensors and wiring

花费了数个世纪 厘清了我们身体的运作机理

so if something does go wrong, they can usually fix it.

因此若是有故障发生， 他们通常能修复我们。

Where they struggle, though, is when the machinery turns on itself-

而令他们苦恼的是， 有时机器人会失控攻击自己——

when a copying error leads a cell to start dividing uncontrollably,

复制中的错误可能会 导致一个细胞不可控制地增殖，

to grow and multiply into a tumor.

成为一个肿瘤。

That's cancer.

那就是癌症。

And sadly, even with the might of our modern medicine,

不幸的是， 即使有了最强大的现代药物，

some cancers evade treatment.

我们依然无法治疗一些癌症。

But this is where a new band of biologists step into the story:

这就是一批崭新的生物学家 施展拳脚的时候了：

The "Synthetic Biologists."

他们就是“合成生物学家”。

These biohackers are mashing up science, medicine and engineering

这些生物黑客融会了 基础科学、医学和工程学

to rewrite the code and fix the un-fixable.

来写出强大的编码修复 难以修复的问题。

Biohackers are going into a patient's genetic code

生物黑客们研究病人的遗传编码

and reprogramming their own immune system

然后改写他们的免疫系统

to recognize cancer cells and destroy them.

使其能够识别出癌变的 细胞并摧毁他们。

It's called CAR T-cell therapy, and it's awesome.

这就是 CAR T-细胞疗法，这很棒。

See, you're constantly under attack by pathogens-

你每时每刻都在受到 病原体的袭击——

single-celled bacteria, viruses and fungi.

单细胞的细菌、病毒和真菌。

Despite deciding, back in the day,

即使这些细胞在过去 决定了要独自行动

to stay solo and not 'avengers assemble' like you did,

而不像你一样“复仇者集结”，

those pathogens see you, in all your mega-meat-bot glory,

它们将你的巨型肉身机器身体

as a fortress ripe for the plundering.

看作一座吸引人的宝藏。

Thankfully, you've got a security team in place to battle these invaders-

还好你有一队安保部队 准备好与这些入侵者战斗——

your immune system-

你的免疫系统——

and some of it's top guards are your white blood cells.

白细胞就是其中的精锐之一。

They trawl the darkness that is your inner space,

它们在你体内游走，

checking the IDs of any cells they pass...

检查他们所遇到 所有细胞的身份……

although they're not name badges,

细胞的身份可不记录在名牌上

but rather protein fragments on the cell's surface called antigens.

而是记录着细胞表面 被称作抗原的蛋白质片段上。

There are two types of these guards: T-cells and B-cells.

白细胞包括了 T-细胞和 B-细胞。

T-cells check those antigen IDs using special claws-

T-细胞用特殊的爪子 检查抗原的身份——

receptors that lock with a particular antigen.

这些爪子回合特定的抗原匹配。

If they find a match, they attach and they release toxic chemicals

要是爪子和抗原匹配成功， 它们会结合并放出有毒的化学物质。

that burst open the invading cell's membrane.

这些化学物质会破坏入侵细胞的细胞膜。

Their B-cell workmates create antibodies-

B-细胞则会生产抗体——

loads of small proteins,

大批的小型蛋白质，

little claws that latch perfectly onto a particular antigen,

这些小蛋白质可以 锁住特定的抗原，

marking them for destruction.

标记它们以便于摧毁。

These two comrades have got your back

这两种保卫者守护着你，

and your immune system is brilliant at spotting and fighting pathogens

而你的免疫系统也善于

that invade from outside.

发现和对抗来自外部的病原体。

However,

they're not so good at spotting your own cells that have gone rogue.

然而，

它们并不擅长对抗 你自己“叛变”的细胞。

The antigens on cancerous cells don't look weird,

癌变的细胞的抗原 看起来并无异样，

they look a lot like your own cells,

就像你自己正常的细胞一样，

and the T's and B's aren't programmed to attack them.

T-细胞和 B-细胞 并不能攻击它们。

The usual way to deal with cancer is to try to cut the tumor out,

通常应对癌症的方法 是切除整个肿瘤，

or turn to radiotherapy and then chemotherapy

或者采用放射疗法和化学疗法

to destroy or block the growth of cancer cells,

来摧毁癌变的细胞 或是抑制其生长，

but if it's a blood cancer, if it's floating around your whole body,

但血癌，即白血病， 会扩散至人的全身，

you can't do that.

就不能应用放射和化学疗法。

And if the blood cancer actually starts in your white blood cells-

若是血癌是源自 你白细胞的癌变——

those key guards in your immune system-

白细胞是免疫系统的 关键组成部分——

you'll really struggle to spot it.

就很难被识别。

That's the case with acute lymphoblastic leukemia,

这就是急性淋巴细胞性白血病，

and that's where CAR T-cell therapy is kicking butt.

正是 CAR T-细胞疗法 大展拳脚的地方。

The biohackers are reprogramming a patient's own immune system

生物黑客们正致力于 改写病人自己的免疫系统

to recognize particular antigens- those particular protein fragments-

来识别出癌变细胞上特定的抗原——

on the cancer cells.

那些特殊的蛋白质片段。

To do it, you first need millions of a patient's T-cells

要做到这点，你首先需要病人 身上数百万的 T-细胞。

Then, to get a T-cell to do something different,

然后，为了更新 T-细胞的功能，

you need to replace its normal code with something new,

你需要改写它原本的编码，

something you've designed.

改成你设计的编码。

What synthetic biologists can now do with DNA is super cool-

合成生物学家改写 DNA 的能力超群，

they use a computer to put together their own sequences of bases-

他们用计算机拼装 特定的碱基序列——

the chemical letters that spell out the DNA-

碱基是构成DNA的化学符号——

then they model what that new genetic code will do on a computer

然后他们在计算机上 模拟新的遗传密码的属性

and then make those sequences on a DNA printer-

最后他们用 DNA 打印机 制成那些序列，

yeah, that's a thing!-

没错，真的有 DNA 打印机！

printing not with ink, or with a plastic polymer like in a 3D printer,

不是用墨水打印，也不是像3D 打印机一样用可塑的聚合物打印，

but with those fundamental building blocks of life,

而使用用那些构成生物的基础，

with those A's and C's and T's and G's.

那些A、C、T 和 G 碱基来打印。

The new code they designed for a T-cell has 3 key instructions:

他们为 T-细胞设计的新密码 有三个关键指示：

1. It tells it how to recognize and kill a cancer cell.

1、这告诉 T-细胞 如何识别并消灭癌变的细胞。

More specifically,

具体来讲，

how to modify an antibody-

如何修改抗体——

what the B-cells make to latch onto a target antigen.

B-细胞制造抗体， 抗体吸附于目标抗原上。

The antibody is modified to make a new receptor

抗体被修改

that can detect the particular antigens on the specific cancer.

使其能够识别特定癌变 细胞上的特殊抗原。

2. It tells it to make copies of itself when it finds that cancer cell

2、告诉 T-细胞在发现 癌变细胞后增值，

and 3. It tells it to survive in the patient's body.

3、告诉 T-细胞在 病人的体内生存。

To get this new code into the patient's T-cells,

为了将这些新的密码 写入病人的 T-细胞，

you use a vector-

要使用一个载体——

it's something that will easily infect the T-cell

载体能轻易感染 T-细胞

and carry that bespoke DNA in with it.

并且能搭载之前所述的 DNA。

And voila! One CAR T-cell.

这样就得到一个 CAR T-细胞了！

The name comes from a fire-breathing monster from Ancient Greece,

此疗法的名字源于 古希腊文化中的一种喷火怪物，

that had a lion's head, a goat's body and a serpent's tail.

它有狮头、羊身和蛇尾。

It was called "Chimera"- a name that has now come to be used

它被称作奇美拉（Chimera），

for something that contains two or more different types of tissues or cells.

现在被用于形容 使用多种组织活细胞的疗法。

As this newly engineered cell's genetic code is part T-cell, part antibody,

CAR T-细胞疗法制造出的新细胞 正是部分 T-细胞，部分抗体，

it's a "C"himera and it goes in search of the cancer's "A"ntigen

它是一种奇美拉，它能够找出 癌变细胞的抗原（Antigen）

using its new "R"eceptor.

用的是它的新接收器（Receptor）。

Before you put the multiplied up T-cells back into the patient,

在你把增殖后的 T-细胞 送回病人体内之前，

you give them a mild dose of chemotherapy to wipe their existing T-cells.

要对病人进行轻微的化学疗法 来消灭体内已有的 T-细胞。

Then you simply reinsert the now modified T-cells-

然后注入修改过的 T-细胞——

the CAR T-cells-

即 CAR T-细胞——

and they follow their normal DNA programming to move and search.

然后它们依据 DNA 编码 来移动和搜寻。

However, thanks to their new butt-kicking code,

和原本的 T-细胞不同，

they've changed what they're looking for:

多亏了修改过的 DNA 编码，

they're now on a mission to find the cancerous cells and destroy them.

它们可以发现并摧毁癌变的细胞。

Unlike conventional chemical-based drugs

传统的化学药物

that get used up or excreted from the body pretty quickly,

在短时间内容易用尽 或是被排出体外，

CAR T-cells are living drugs that stay in the patient's bloodstream for years.

而 CAR T-细胞是活的药物， 能够在病人的血液循环中保留数年。

That's a huge pro.

这是个巨大的优点。

The flip side is that they're expensive-

而缺点是此疗法很昂贵——

each CAR T-cell treatment is bespoke to the patient-

每次 CAR T-细胞疗法 都要为病人定制——

and it's more difficult to get them to work with common cancers

因此很难将其用于一般的癌症 如乳腺癌和肺癌，

like breast or lung, because you need a specific antigen on the cancer cells

因为此疗法需要癌变 细胞上特定的抗原

for the CAR T-cell to target-

来作为 CAR T-细胞的目标——

and it's much easier to find that in blood cancers.

而这些抗原在血癌中 则更容易获得。

It's still early days, though,

不过 CAR T-细胞疗法还在初级阶段，

and there's an exciting future for CAR T-cell therapy.

它的未来应用前景十分明朗。

Researchers like Dr. Martin Pule and his team at UCL,

一些科学家，如马丁 · 普莱博士和 他在伦敦大学学院的团队，

are working on improving the leukemia and lymphoma treatments even further,

正在致力于推进白血病 和淋巴瘤的治疗，

and there's recently been some promising work on solid cancers.

最近针对固态瘤的研究 也有很大的进展。

Thanks to CAR T-cell therapy,

因为 CAR T-细胞疗法，

the survival rate for B acute lymphoblastic leukemia has improved hugely

急性 B 细胞白血病的 生还率显著增加，

-nearly all patients go into remission-

几乎所有的患者的 症状都能得到缓解，

which means that leukemia cannot be detected anymore-

这些病人的体内不再 被检测出白血病，

and most patients stay in remission.

而且大部分病人都能保持在缓解的状态。

Biohacking is here,

生物黑客技术已成现实，

and it can reprogram your own genetic code to enable your mega-meat-bot

使人们可以改写基因编码， 使得你的巨型肉身机器

to do things it's never been able to do before!

做到之前无法做到的事！