Hacking bacteria to fight cancer - Tal Danino

翻译人员: Yue WANG 校对人员: Jiasi Hao

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

1884 年，一位癌症患者的病情每况愈下。

This patient had a rapidly growing cancer in his neck,

他颈部的恶性肿瘤快速增大，

and then came down with an unrelated bacterial skin infection.

随之而来的，是非肿瘤所致的 细菌性皮肤感染。

But soon, something unexpected happened:

但很快，令人意外的情况出现了：

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

随着此人皮肤感染的痊愈， 他的恶性肿瘤亦开始消退。

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

一位名叫威廉 · 科利的医生（William Coley） 在 7 年后找到这名患者，

no visible signs of the cancer remained.

他没有发现任何 癌症（恶性肿瘤）遗存的迹象。

Coley believed something remarkable was happening:

科利于是相信 有一件举世瞩目的事情要发生：

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

细菌感染能够刺激患者的免疫系统

to fight off the cancer.

以对抗癌症。

Coley’s fortunate discovery led him to pioneer

这项发现使科利成为癌症疗法的先驱，

the intentional injection of bacteria to successfully treat cancer.

即，有意向患者体内注射细菌， 以成功治疗癌症。

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

一个世纪之后， 合成生物学家发现了更好的治疗手段。

to use these once unlikely allies—

他们利用了看似不可能的盟友——

by programming them to safely deliver drugs directly to tumors.

通过人为编程细菌的帮助， 使药物安全并直接地送至肿瘤处。

Cancer occurs when normal functions of cells are altered,

当细胞正常功能被改变时， 癌症就会发生。

causing them to rapidly multiply and form growths called tumors.

癌变细胞之后开始 快速繁殖、成长，最终形成肿瘤。

Treatments like radiation, chemotherapy, and immunotherapy

诸如放疗、化疗以及免疫疗法

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

会击杀癌细胞， 但对整个身体也有副作用，

and disrupt healthy tissues in the process.

而且会在治疗过程中 无差别地破坏健康的组织。

However, some bacteria like E. coli

然而，一些细菌，例如大肠杆菌

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

具有特定的优势， 它们可以选择性地在肿瘤内生长。

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

实际上，肿瘤的内部核心 为细菌提供了理想的生长环境，

where they can safely multiply, hidden from immune cells.

供细菌安全地繁殖， 躲避免疫细胞的攻击。

Instead of causing infection,

这样的细菌不但不会引发炎症

bacteria can be reprogrammed to carry cancer-fighting drugs,

还可被重编程， 使其自身携带抗癌药物

acting as Trojan Horses that target the tumor from within.

犹如特洛伊木马， 从肿瘤内部展开攻击。

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

此类通过基因编程细菌活细胞 作为治疗手段的新颖方式

is a major focus of a field called Synthetic Biology.

是目前合成生物学中 一个备受关注的领域。

But how can bacteria be programmed?

那细菌是如何被编程的呢？

The key lies in manipulating their DNA.

关键就在于对它们 DNA 的操控。

By inserting particular genetic sequences into bacteria,

在细菌活细胞的 DNA 中 插入特别的基因序列，

they can be instructed to synthesize different molecules,

并指导其合成不同的分子。

including those that disrupt cancer growth.

其中包括一些 会干扰癌细胞的生长的分子。

They can also be made to behave in very specific ways

在生物电路的帮助下，

with the help of biological circuits.

细菌还可以被编程， 从而做出特定行为。

These program different behaviors depending on the presence, absence,

这些行为基于特定因素的 出现、缺失或组合而异。

or combination of certain factors.

For example, tumors have low oxygen and pH levels

举个例子，肿瘤通常 含氧量低， PH 值低，

and over-produce specific molecules.

并且会过量生产特定分子。

Synthetic biologists can program bacteria to sense those conditions,

合成生物学家们 可以让细菌对这些条件敏感，

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

因此使得细菌只对肿瘤反应， 从而避开健康组织。

One type of biological circuit,

有一种生物电路， 名为同步裂解回路（SLC）。

known as a synchronized lysis circuit, or SLC,

allows bacteria to not only deliver medicine,

它不仅能使细菌携带药物， 还可使其按时间规律行动。

but to do so on a set schedule.

First, to avoid harming healthy tissue,

首先，为避免伤害健康组织，

production of anti-cancer drugs begins as bacteria grow,

抗癌药物会随着细菌的生长被释放，

which only happens within the tumor itself.

而整个过程仅会发生在肿瘤内部。

Next, after they’ve produced the drugs,

接下来，在药物被释放完毕后，

a kill-switch causes the bacteria to burst

当细菌数量上升至临界值时，

when they reach a critical population threshold.

一个生死 开关会被启动， 致使细菌爆裂。

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

这样既释放了药物， 又削减了细菌数量。

However, a certain percentage of the bacteria remain alive

当然，一定比例的细菌会存活下来

to replenish the colony.

以待继续繁殖、占领肿瘤。

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

最终，细菌的数量将再次 增长至临界值，触发生死开关，

and the cycle continues.

如此循环。

This circuit can be fine-tuned to deliver drugs

人们可将生物电路中 药物释放的周期进行微调，

on whatever periodic schedule is best to fight the cancer.

以最佳方式对抗不同癌症。

This approach has proven promising in scientific trials using mice.

这一治疗方法已在科学实验中的 小白鼠身上被证实具有前景。

Not only were scientists able to successfully eliminate lymphoma tumors

科学家通过注射细菌， 不仅可以消灭淋巴瘤，

injected with bacteria,

同时还会刺激免疫系统，

but the injection also stimulated the immune system,

priming immune cells to identify and attack untreated lymphomas

引发免疫细胞识别并攻击

elsewhere in the mouse.

实验鼠体内 其他未受药物影响的淋巴瘤。

Unlike many other therapies,

不同于其他疗法， 细菌并非只针对一种癌细胞，

bacteria don’t target a specific type of cancer,

but rather the general characteristics shared by all solid tumors.

而是以实体瘤的 一些共有特征作为靶点。

Nor are programmable bacteria limited to simply fighting cancer.

被基因编辑过的细菌 不局限于简单的对抗癌症，

Instead, they can serve as sophisticated sensors

同时，还能作为复杂精密的感应器

that monitor sites of future disease.

以监视未来疾病的发生部位。

Safe probiotic bacteria could perhaps lie dormant within our guts,

安全的益生菌甚至 能以休眠状态潜伏于内脏，

where they’d detect, prevent, and treat disorders

在任何体内失调可能导致 疾病症状发生之前，

before they have the chance to cause symptoms.

进行探测、阻止及治疗。

Advances in technology have created excitement around a future

科技的发展，例如未来将会出现的

of personalized medicine driven by mechanical nanobots.

能带来更多个性化药物的纳米机器人， 令人兴奋无比。

But thanks to billions of years of evolution

不过多亏了数亿年来的进化，

we may already have a starting point

我们可能已经站在了

in the unexpectedly biological form of bacteria.

研究细菌全新生物形态的起点。

Add synthetic biology to the mix,

向其中融入合成生物学，

and who knows what might soon be possible.

谁人可知未来的可能呢？