In 1884, a patient’s luck seemed to go from bad to worse. This patient had a rapidly growing cancer in his neck, and then came down with an unrelated bacterial skin infection. But soon, something unexpected happened: as he recovered from the infection, the cancer also began to recede. When a physician named William Coley tracked the patient down 7 years later, no visible signs of the cancer remained. Coley believed something remarkable was happening: that the bacterial infection had stimulated the patient’s immune system to fight off the cancer.
1884 年,一位癌症患者的病情每况愈下。 他颈部的恶性肿瘤快速增大, 随之而来的,是非肿瘤所致的 细菌性皮肤感染。 但很快,令人意外的情况出现了: 随着此人皮肤感染的痊愈, 他的恶性肿瘤亦开始消退。 一位名叫威廉 · 科利的医生(William Coley) 在 7 年后找到这名患者, 他没有发现任何 癌症(恶性肿瘤)遗存的迹象。 科利于是相信 有一件举世瞩目的事情要发生: 细菌感染能够刺激患者的免疫系统 以对抗癌症。
Coley’s fortunate discovery led him to pioneer the intentional injection of bacteria to successfully treat cancer. Over a century later, synthetic biologists have found an even better way to use these once unlikely allies— by programming them to safely deliver drugs directly to tumors.
这项发现使科利成为癌症疗法的先驱, 即,有意向患者体内注射细菌, 以成功治疗癌症。 一个世纪之后, 合成生物学家发现了更好的治疗手段。 他们利用了看似不可能的盟友—— 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, causing them to rapidly multiply and form growths called tumors. Treatments like radiation, chemotherapy, and immunotherapy attempt to kill malignant cells, but can affect the entire body and disrupt healthy tissues in the process.
当细胞正常功能被改变时, 癌症就会发生。 癌变细胞之后开始 快速繁殖、成长,最终形成肿瘤。 诸如放疗、化疗以及免疫疗法 会击杀癌细胞, 但对整个身体也有副作用, 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 have the unique advantage of being able to selectively grow inside tumors. In fact, the core of a tumor forms an ideal environment where they can safely multiply, hidden from immune cells. Instead of causing infection, bacteria can be reprogrammed to carry cancer-fighting drugs, acting as Trojan Horses that target the tumor from within. This idea of programming bacteria to sense and respond in novel ways is a major focus of a field called Synthetic Biology.
然而,一些细菌,例如大肠杆菌 具有特定的优势, 它们可以选择性地在肿瘤内生长。 实际上,肿瘤的内部核心 为细菌提供了理想的生长环境, 供细菌安全地繁殖, 躲避免疫细胞的攻击。 这样的细菌不但不会引发炎症 还可被重编程, 使其自身携带抗癌药物 犹如特洛伊木马, 从肿瘤内部展开攻击。 此类通过基因编程细菌活细胞 作为治疗手段的新颖方式 是目前合成生物学中 一个备受关注的领域。
But how can bacteria be programmed? The key lies in manipulating their DNA. By inserting particular genetic sequences into bacteria, they can be instructed to synthesize different molecules, including those that disrupt cancer growth. They can also be made to behave in very specific ways with the help of biological circuits. These program different behaviors depending on the presence, absence, or combination of certain factors. For example, tumors have low oxygen and pH levels and over-produce specific molecules. Synthetic biologists can program bacteria to sense those conditions, and by doing so, respond to tumors while avoiding healthy tissue.
那细菌是如何被编程的呢? 关键就在于对它们 DNA 的操控。 在细菌活细胞的 DNA 中 插入特别的基因序列, 并指导其合成不同的分子。 其中包括一些 会干扰癌细胞的生长的分子。 在生物电路的帮助下, 细菌还可以被编程, 从而做出特定行为。 这些行为基于特定因素的 出现、缺失或组合而异。 举个例子,肿瘤通常 含氧量低, PH 值低, 并且会过量生产特定分子。 合成生物学家们 可以让细菌对这些条件敏感, 因此使得细菌只对肿瘤反应, 从而避开健康组织。 有一种生物电路, 名为同步裂解回路(SLC)。
One type of biological circuit, known as a synchronized lysis circuit, or SLC, allows bacteria to not only deliver medicine, but to do so on a set schedule. First, to avoid harming healthy tissue, production of anti-cancer drugs begins as bacteria grow, which only happens within the tumor itself. Next, after they’ve produced the drugs, a kill-switch causes the bacteria to burst when they reach a critical population threshold. This both releases the medicine and decreases the bacteria’s population. However, a certain percentage of the bacteria remain alive to replenish the colony. Eventually their numbers grow large enough to trigger the kill switch again, and the cycle continues. This circuit can be fine-tuned to deliver drugs on whatever periodic schedule is best to fight the cancer.
它不仅能使细菌携带药物, 还可使其按时间规律行动。 首先,为避免伤害健康组织, 抗癌药物会随着细菌的生长被释放, 而整个过程仅会发生在肿瘤内部。 接下来,在药物被释放完毕后, 当细菌数量上升至临界值时, 一个生死 开关会被启动, 致使细菌爆裂。 这样既释放了药物, 又削减了细菌数量。 当然,一定比例的细菌会存活下来 以待继续繁殖、占领肿瘤。 最终,细菌的数量将再次 增长至临界值,触发生死开关, 如此循环。 人们可将生物电路中 药物释放的周期进行微调, 以最佳方式对抗不同癌症。
This approach has proven promising in scientific trials using mice. Not only were scientists able to successfully eliminate lymphoma tumors injected with bacteria, but the injection also stimulated the immune system, priming immune cells to identify and attack untreated lymphomas elsewhere in the mouse.
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。 科学家通过注射细菌, 不仅可以消灭淋巴瘤, 同时还会刺激免疫系统, 引发免疫细胞识别并攻击 实验鼠体内 其他未受药物影响的淋巴瘤。 不同于其他疗法, 细菌并非只针对一种癌细胞,
Unlike many other therapies, bacteria don’t target a specific type of cancer, but rather the general characteristics shared by all solid tumors. Nor are programmable bacteria limited to simply fighting cancer. Instead, they can serve as sophisticated sensors that monitor sites of future disease. Safe probiotic bacteria could perhaps lie dormant within our guts, where they’d detect, prevent, and treat disorders before they have the chance to cause symptoms.
而是以实体瘤的 一些共有特征作为靶点。 被基因编辑过的细菌 不局限于简单的对抗癌症, 同时,还能作为复杂精密的感应器 以监视未来疾病的发生部位。 安全的益生菌甚至 能以休眠状态潜伏于内脏, 在任何体内失调可能导致 疾病症状发生之前, 进行探测、阻止及治疗。 科技的发展,例如未来将会出现的
Advances in technology have created excitement around a future of personalized medicine driven by mechanical nanobots. But thanks to billions of years of evolution we may already have a starting point in the unexpectedly biological form of bacteria. Add synthetic biology to the mix, and who knows what might soon be possible.
能带来更多个性化药物的纳米机器人, 令人兴奋无比。 不过多亏了数亿年来的进化, 我们可能已经站在了 研究细菌全新生物形态的起点。 向其中融入合成生物学, 谁人可知未来的可能呢?