How to biohack your cells to fight cancer - Greg Foot

譯者: Lilian Chiu 審譯者: Helen Chang

Ok, so you,

好，所以，

are a 4 billion year old meat robot.

你是十億歲的肉製機器人。

Yeah, you heard me right.

是的，你沒聽錯。

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

事實上，你是由 三十多兆個細胞組成的，

and each of those have their own task,

每個細胞都有它自己的任務，

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

你是個機器人，由數兆個 迷你機器人組成——

you are a mega-meat-bot!

你是個超級肉製機器人！

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

你的使命，在過去四十億年左右，

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

只要你繼續參與這場生命遊戲，

is to safeguard the code.

就得進行的使命是要保護編碼。

To duplicate it. To pass it on.

要複製它，將它傳下去。

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

重點是，你實在很不擅長 複製你自己的編碼。

Every time it's copied, errors crop up.

每次複製時，就會發生錯誤。

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

當錯誤會讓機器人的生存能力 變差時，並不是好事，

but sometimes a mistake helps them survive...

但有時候，錯誤能協助它們生存……

and they pass that glitch in the code on-

它們會把編碼中的 這個小問題傳下去——

that's evolution in a nutshell, right?

概括地說，那就是演化，對吧？

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

這恐怕就意味著，你並不是 酷炫設計出來的結果。

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

你是數十億年做爛的複製品 所產生的結果。

Go you.

幹得好。

Another reason you're not totally awesome

還有一個理由可以說明 你不是那麼讚，

is because that megabot of yours often breaks down.

因為你的那個 超級機器人常常會失靈。

Fortunately,

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

幸運的是，心臟病學家、免疫學家、

微生物學家——各種學家——

have spent centuries figuring out our sensors and wiring

花了數世紀的時間去了解 我們的感測器和線路，

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

所以有什麼地方出錯時， 他們通常都可以修復。

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

但，會讓他們很費力的就是 機器自行啟動的情況——

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

也就是複製錯誤造成細胞 開始不受控制地分裂、

to grow and multiply into a tumor.

成長、繁殖，成為腫瘤。

That's cancer.

那就是癌症。

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

不幸的是，即使現代醫學威力強大，

some cancers evade treatment.

有些癌症仍然可以躲過治療。

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

但，此時就要輪到 一群生物學家登場了：

The "Synthetic Biologists."

「合成生物學家」。

These biohackers are mashing up science, medicine and engineering

這些生物駭客會把科學、 醫學，以及工程給混合起來，

to rewrite the code and fix the un-fixable.

重新寫過編碼， 把不能修好的部分修好。

Biohackers are going into a patient's genetic code

生物駭客會進入病人的基因編碼中，

and reprogramming their own immune system

並重新寫他們自己的免疫系統，

to recognize cancer cells and destroy them.

來識別出癌症細胞，並將之消滅。

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

這就是 CAR T 細胞療法，它很棒。

See, you're constantly under attack by pathogens-

你常常會受到病原體的攻擊——

single-celled bacteria, viruses and fungi.

單細胞的細菌、病毒、真菌。

Despite deciding, back in the day,

儘管早些時候 那些病原體決定要持續單飛，

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

不像你是「復仇者集合」，

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

但它們把你這個 壯觀的超級肉製機器人，

as a fortress ripe for the plundering.

視為是很適合劫掠的堡壘。

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

謝天謝地，你還有個準備好 對抗這些入侵者的保安團隊——

your immune system-

你的免疫系統——

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

團隊中的頂尖警衛 就是你的白血球細胞。

They trawl the darkness that is your inner space,

它們在黑暗（也就是 你的內在空間）中捕獵，

checking the IDs of any cells they pass...

只要遇到任何細胞， 就會上前確認它的身分，

although they're not name badges,

不過身分指的不是名牌，

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

而是細胞表面的 蛋白質片段，稱為抗原。

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

警衛有兩類：T 細胞和 B 細胞。

T-cells check those antigen IDs using special claws-

T 細胞會用特殊的爪子 去檢查那些抗原的身分——

receptors that lock with a particular antigen.

爪子指的是鎖定特定抗原的接收器。

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

如果發現符合的對象，它們就會 附著上去，釋出有毒化學物質，

that burst open the invading cell's membrane.

讓入侵細胞的細胞膜爆裂。

Their B-cell workmates create antibodies-

它們的工作夥伴 B 細胞會創造抗體——

loads of small proteins,

即一大堆的小蛋白質，

little claws that latch perfectly onto a particular antigen,

可以完美鎖上特定抗原的小爪子，

marking them for destruction.

做上「要摧毀的目標」記號。

These two comrades have got your back

你背後有這兩位同志撐腰，

and your immune system is brilliant at spotting and fighting pathogens

你的免疫系統很擅長 發現從外界入侵的病原體，

that invade from outside.

並對抗它們。

However,

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

然而，

如果是你自己的細胞叛變了， 就不見得會被它們發現。

The antigens on cancerous cells don't look weird,

癌症細胞上的抗原看起來並不奇怪，

they look a lot like your own cells,

它們看起來很像你自己的細胞，

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

T 細胞和 B 細胞 不是設計來攻擊它們的。

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

要處理癌症，一般的 做法是把腫瘤切除，

or turn to radiotherapy and then chemotherapy

或是做放射線治療， 接著是化學療法，

to destroy or block the growth of cancer cells,

以摧毀癌症細胞或阻止它們成長，

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

但，如果是血癌，如果 癌細胞在你全身四處流動，

you can't do that.

就不能這麼做了。

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

如果血癌始於你的白血球細胞——

those key guards in your immune system-

也就是你的免疫系統的重要警衛——

you'll really struggle to spot it.

就會真的很難發現得了血癌。

That's the case with acute lymphoblastic leukemia,

急性淋巴性白血病就是如此，

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

那就是 CAR T 細胞療法 能大顯身手的時候了。

The biohackers are reprogramming a patient's own immune system

這些生物駭客會為病人 自己的免疫系統重新編碼，

to recognize particular antigens- those particular protein fragments-

讓它能識別出 癌症細胞上的特定抗原——

on the cancer cells.

那些特定的蛋白質片段。

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

如果要做這種治療，你首先 需要病人的數百萬個 T 細胞，

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

接著，要讓 T 細胞去做不同的事，

you need to replace its normal code with something new,

就得要把它的正常編碼 換成新的編碼，

something you've designed.

換成你設計的編碼。

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

現今，合成生物學家用 DNA 能夠做到非常酷的事——

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

他們會用電腦來拼湊 他們自己的基礎序列——

the chemical letters that spell out the DNA-

即拼出 DNA 的化學字母——

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

接著，他們用電腦建模， 模擬新的基因碼能夠做什麼，

and then make those sequences on a DNA printer-

接著用 DNA 印表機 來做出那些序列——

yeah, that's a thing!-

對，DNA 能印出來——

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

不是用墨水來印，也不是 像 3D 印表機用塑料聚合物來印，

but with those fundamental building blocks of life,

而是用生命的基礎建材來印，

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

也就是 A、C、T、G 這些字母。

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

他們為 T 細胞設計的新編碼 會帶有三項重要指令：

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

一、編碼會告訴 T 細胞 如何識別和殺死癌症細胞。

More specifically,

更明確來說，就是 如何修改抗體——

how to modify an antibody-

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

B 細胞要製造什麼 來鎖住目標抗原。

The antibody is modified to make a new receptor

抗體被修改後， 會製造出新的接收器，

that can detect the particular antigens on the specific cancer.

來偵測某種癌症上的特定抗原。

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

二、編碼會叫 T 細胞在找到 那種癌症細胞時，進行自我複製，

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

三、編碼會教 T 細胞 在病人的身體中存活。

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

要把這種新編碼 放到病人的 T 細胞中，

you use a vector-

得要用向量——

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

它很容易感染 T 細胞，

and carry that bespoke DNA in with it.

且會隨身帶著訂製的 DNA。

And voila! One CAR T-cell.

然後，看哪！一個 CAR T 細胞。

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

這個名字來自古希臘的噴火怪獸，

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

牠有獅子的頭、 山羊的身體、蛇的尾巴。

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

牠被稱為「喀邁拉」，現在 這個詞已經漸漸被用來意指

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

含有兩種以上不同型 組織或細胞的東西。

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

因為這種新設計細胞的基因碼 有部分是 T 細胞、部分是抗體，

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

它就是喀邁拉（C 開頭），它會去 尋找癌症的抗原（A 開頭），

using its new "R"eceptor.

用的是它的新接收器（R 開頭）。

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

在你把繁殖出來的 T 細胞 放回病人身上之前，

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

要先讓病人進行微量的化學療法， 把他們既有的 T 細胞消滅。

Then you simply reinsert the now modified T-cells-

接著，你就只要重新置入 修改過的新 T 細胞——

the CAR T-cells-

CAR T 細胞——

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

它們就會遵循它們一般的 DNA 編碼來移動和探尋。

However, thanks to their new butt-kicking code,

然而，因為有它們的超殺新編碼，

they've changed what they're looking for:

它們會改變尋找的目標：

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

現在，它們的任務 是要找到並摧毀癌細胞。

Unlike conventional chemical-based drugs

傳統的化學藥物

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

很會就會用盡或是被排出體外，

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

CAR T 細胞不同， 它們是活的藥物，

可以留在病人的血液中數年之久。

That's a huge pro.

那是個很大的優點。

The flip side is that they're expensive-

缺點則是它們很昂貴——

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

CAR T 細胞治法都是 為病人訂製的——

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

且不太容易把它們 用在一般的癌症上，

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

比如乳癌或肺癌，因為癌細胞 上面需要有明確的抗原

for the CAR T-cell to target-

來當作 CAR T 細胞的目標——

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

在血癌中找出這種抗原就容易許多。

It's still early days, though,

不過，現在還是初期，

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

CAR T 細胞療法 有著讓人興奮的未來。

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

有些研究者，如馬丁普爾 和他在倫敦大學學院的團隊，

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

在努力進一步改善 白血病和淋巴瘤的治療，

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

近期，針對固態瘤， 也有一些前景看好的研究。

Thanks to CAR T-cell therapy,

因為有 CAR T 療法，

the survival rate for B acute lymphoblastic leukemia has improved hugely

B 細胞急性淋巴性白血病的 存活率大大改善了——

-nearly all patients go into remission-

幾乎所有病人都能得到緩解——

which means that leukemia cannot be detected anymore-

這就意味著，無法 再偵測到白血病了——

and most patients stay in remission.

且大部分病人 會保持在緩解的狀態。

Biohacking is here,

生物駭客技術來了，

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

它能夠為你自己的基因重新編碼， 讓你的超級肉製機器人

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

去做它以前無法做到的事！