Hacking bacteria to fight cancer - Tal Danino

譯者: Lilian Chiu 審譯者: Helen Chang

In 1884, a patient’s luck seemed to go from bad to worse.

1884 年，有一位病人的運氣 似乎從很差變成更差了。

This patient had a rapidly growing cancer in his neck,

這位病人的脖子上 長了個快速成長的腫瘤，

and then came down with an unrelated bacterial skin infection.

接著，又染上了不相關的 細菌性皮膚感染。

But soon, something unexpected happened:

但，很快的，未預期的事發生了：

as he recovered from the infection, the cancer also began to recede.

當他從感染中復元時， 癌症也開始減緩。

When a physician named William Coley tracked the patient down 7 years later,

醫生威廉科萊在七年後 追蹤這位病人，

no visible signs of the cancer remained.

發現已經沒剩下任何 可見的癌症徵象。

Coley believed something remarkable was happening:

科萊相信這位病人身上 發生了很不凡的事：

that the bacterial infection had stimulated the patient’s immune system

細菌感染刺激了病人的免疫系統，

to fight off the cancer.

將癌症擊退。

Coley’s fortunate discovery led him to pioneer

科萊幸運的發現讓他成為先驅，

the intentional injection of bacteria to successfully treat cancer.

倡導刻意注射細菌以成功治療癌症。

Over a century later, synthetic biologists have found an even better way

一百多年後，合成生物學家 發現了更好的方式

to use these once unlikely allies—

來使用這些以前 無法想像的盟友——

by programming them to safely deliver drugs directly to tumors.

透過編程，讓細菌將藥物 安全地送到腫瘤所在處。

Cancer occurs when normal functions of cells are altered,

癌症的成因，是因為 細胞的正常功能受到改變，

causing them to rapidly multiply and form growths called tumors.

導致它們快速增加， 形成叫做「腫瘤」的贅生物。

Treatments like radiation, chemotherapy, and immunotherapy

放射線治療、化療、 免疫療法等治療方法

attempt to kill malignant cells, but can affect the entire body

都是在嘗試殺死惡性細胞， 但可能會影響整個身體，

and disrupt healthy tissues in the process.

在過程中破壞了健康的組織。

However, some bacteria like E. coli

然而，有些細菌，像大腸桿菌，

have the unique advantage of being able to selectively grow inside tumors.

具有獨特的優勢，它們能夠 選擇性地在腫瘤中生長。

In fact, the core of a tumor forms an ideal environment

事實上，腫瘤的核心 反而是個理想的環境，

where they can safely multiply, hidden from immune cells.

讓大腸桿菌能夠避開 免疫細胞，安全增長。

Instead of causing infection,

細菌可以被重新編程，

bacteria can be reprogrammed to carry cancer-fighting drugs,

讓它們不會造成感染， 且能夠攜帶抗癌藥物，

acting as Trojan Horses that target the tumor from within.

扮演特洛伊木馬，從腫瘤內部進攻。

This idea of programming bacteria to sense and respond in novel ways

透過細菌編程讓細菌 做出新穎的感覺和反應，

is a major focus of a field called Synthetic Biology.

這個點子是合成生物學 領域的主要焦點之一。

But how can bacteria be programmed?

但要怎麼做細菌編程呢？

The key lies in manipulating their DNA.

關鍵在於操控細菌的 DNA。

By inserting particular genetic sequences into bacteria,

將特定的基因序列插入到細菌中，

they can be instructed to synthesize different molecules,

細菌就能接受指示， 合成不同的分子，

including those that disrupt cancer growth.

包括能夠打斷癌症生長的分子。

They can also be made to behave in very specific ways

在生物電路的協助之下，

也可以讓細菌做出 非常明確的特定行為。

with the help of biological circuits.

These program different behaviors depending on the presence, absence,

生物電路可以根據存在、 不存在，或某些因子的組合，

or combination of certain factors.

來做不同的行為編程。

For example, tumors have low oxygen and pH levels

比如，腫瘤的含氧量 及 pH 值都很低，

and over-produce specific molecules.

且會過度生產特定的分子。

Synthetic biologists can program bacteria to sense those conditions,

合成生物學家可透過編程， 讓細菌感測到那些條件，

and by doing so, respond to tumors while avoiding healthy tissue.

因此就能夠針對腫瘤 做出反應，避開健康組織。

One type of biological circuit,

有一種生物電路

known as a synchronized lysis circuit, or SLC,

叫做同步裂解電路（SLC），

allows bacteria to not only deliver medicine,

不僅能讓細菌去遞送藥物， 還能依時間表排程遞送。

but to do so on a set schedule.

First, to avoid harming healthy tissue,

首先，為了避免傷害到健康組織，

production of anti-cancer drugs begins as bacteria grow,

在細菌生長時才開始 製造抗癌藥物，

which only happens within the tumor itself.

因為細菌生長只會 在腫瘤內部發生。

Next, after they’ve produced the drugs,

接著，在細菌製造了藥物之後，

a kill-switch causes the bacteria to burst

當細菌的數量到達臨界值時，

when they reach a critical population threshold.

緊急停止開關會造成細菌爆裂。

This both releases the medicine and decreases the bacteria’s population.

爆裂後釋出藥物也減少細菌的數量。

However, a certain percentage of the bacteria remain alive

然而有一定比例的細菌仍然活著，

to replenish the colony.

可以讓菌落繼續成長。

Eventually their numbers grow large enough to trigger the kill switch again,

最終，細菌的數量又大到 會再次觸發緊急停止開關，

and the cycle continues.

不斷重覆循環。

This circuit can be fine-tuned to deliver drugs

這種電路可做精確調整，

依據最適合用來對抗癌症的 固定排程來遞送藥物。

on whatever periodic schedule is best to fight the cancer.

This approach has proven promising in scientific trials using mice.

在用老鼠的科學試驗中， 已經證明這個方法很有希望。

Not only were scientists able to successfully eliminate lymphoma tumors

科學家不僅能夠成功

透過注入細菌的方式消除淋巴瘤，

injected with bacteria,

but the injection also stimulated the immune system,

同時也能刺激免疫系統，

priming immune cells to identify and attack untreated lymphomas

指導免疫細胞去辨視並攻擊 在老鼠體內其他地方

elsewhere in the mouse.

沒有被治療到的淋巴瘤。

Unlike many other therapies,

和許多其他治療方法不同， 細菌不會針對特定的癌症類型，

bacteria don’t target a specific type of cancer,

but rather the general characteristics shared by all solid tumors.

而是去找所有實質固態瘤 共同的一般性特徵。

Nor are programmable bacteria limited to simply fighting cancer.

可編程的細菌也不限用在對抗癌症，

Instead, they can serve as sophisticated sensors

還可以被當作精密的感測器，

that monitor sites of future disease.

監視未來疾病的所在。

Safe probiotic bacteria could perhaps lie dormant within our guts,

安全的益生菌或許能在 我們的腸道中休眠，

where they’d detect, prevent, and treat disorders

在那裡，它們可以偵測、 預防、治療疾病，

before they have the chance to cause symptoms.

讓它們沒機會造成任何症狀。

Advances in technology have created excitement around a future

科技的進步讓大家 很興奮地預期在未來

of personalized medicine driven by mechanical nanobots.

由機械奈米機器人 遞送個人化的藥物。

But thanks to billions of years of evolution

但，因為有數十億年的演化，

we may already have a starting point

我們可能已經在 未預期的細菌生物形式中

in the unexpectedly biological form of bacteria.

找到了一個起始點。

Add synthetic biology to the mix,

再把合成生物學也加進來，

and who knows what might soon be possible.

天知道不久後還會出現 什麼新的可能性。