Programmed Bacteria Can Detect Tumors

微生物诊断肿瘤

Sangeeta Bhatia of M.I.T. talks about efforts to get bacteria to home in on tumors and let us know they're there. Cynthia Graber reports

麻省理工学院的桑吉塔·巴蒂亚为我们描述了如何利用微生物确定肿瘤的存在。

撰文/播音  辛西亚·格雷伯（Cynthia Graber）

翻译  李轩

Probiotics are hot. Bacteria that we consume in foods like yogurt, miso and pickles can help our gut microbiomes stay happy and healthy. Now there might be another role for those probiotic bacteria: cancer detection. Two papers in the journal Science Translational Medicine explain how researchers hope to get bacteria to be diagnostic tools. [Tal Danino et al,Programmable probiotics for detection of cancer in urine], [Alexis Courbet et al,Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates]

益生菌一直倍受欢迎。这些我们加进酸奶、味噌与腌菜中的微生物可以促进我们肠道菌落的平衡与健康。如今，它们或许有了另外一个角色：探测癌症。两篇发表在《科学转化医学》期刊上的研究为我们展示了研究人员将如何使这些微生物转化成诊断工具。

Sangeeta Bhatia of M.I.T. is a liver expert and senior author of one of the papers. Her lab had been trying to figure out how to get nanoparticles to the liver that would send a signal detectable in urine if they encountered a tumor. Cancers that start in the colon or pancreas can metastasize to the liver, which can be deadly.

桑吉塔·巴蒂亚是麻省理工学院的肝脏专家以及其中一篇论文的资深作者。她的实验室一直在尝试如何利用送入肝脏纳米粒子，在尿液中显现肿瘤信息。发生在结肠与胰腺的癌症有时会转移至肝脏，这将是致命的。

SB: “And one of the students on the team had the idea that if you can imagine that there's a material, a diagnostic material, that would grow itself then you wouldn’t need very much of it to arrive at the tumor and sort of self-amplify. And we realized that bacteria are in many ways just such a device. That they can naturally home in on tumors…so we thought maybe we can hijack that ability of bacteria to home in on tumors and self-amplify to create a urinary diagnostic.”

巴蒂亚：“我们团队中的一个学生曾经有过一个想法，所需要的是一种可以自我生长的诊断材料，这样你就不需要将过多的材料送至肿瘤处。我们觉得微生物在某种程度上正是这样一种材料，它们可以在肿瘤内部生长，所以我们认为可以赋予微生物这种能力，让它可以在肿瘤内部安家并自行生长，从而在尿液中有所反映。”

Bhatia’s lab teamed up with a lab at the University of California, San Diego, with expertise in synthetic biology—basically altering microbes to have specific functions.

巴蒂亚的实验室与加州大学圣地亚哥分校的一个实验室进行了合作，利用合成生物学的技术，对微生物进行改造。

SB: “So instead of just going out and finding natural strains that would colonize tumors and do what wanted, we could pick strains that have good homing and then endow them with the capabilities that we were interested in.”

巴蒂亚：“我们并没有去自然界中寻找与肿瘤亲和及可以满足我们要求的微生物，而是对实验室的菌株进行改造，赋予它们我想想要的能力。”

The two labs took a strain of E. coli called Nissle that is already used as a probiotic to help people with digestive issues. They programmed the bacteria to express a specific enzyme after it occupied liver tumors. If the bacteria colonized a tumor in mice, the mice would produce urine that, thanks to the enzyme, would turn red.

这两个实验室使用了尼氏大肠杆菌，它是一种可以用于解决消化问题的益生菌。他们改造了它，使得它着陆在肿瘤上后可以表达特定的酶。如果这种微生物附着在了小鼠体内的肿瘤上，它产生的酶将会使小鼠的尿液变红。

The system worked—the bacteria found tumors in mice known to have them, and the urine changed color, indicating the presence of cancer. Cancer-free mice that also ate the engineered probiotics showed no negative health effects a year later.

这个系统确实起作用了——在已知有肿瘤的小鼠身上实验，它们的尿液的确会变色，暗示体内有肿瘤存在。而服用转基因益生菌的小鼠在1年之后也没有出现副作用。

The technique is at this stage just a proof of concept, says Bhatia. But it’s got a lot of promise.

巴蒂亚说，这种技术目前还处在理论证明阶段，不过它有着广阔的前景。

SB: “Well what we're really excited about the idea that you can take synthetic biology some day into both diagnostics and also therapeutics. So in this particular case the circuit that we put the bacteria gave off a diagnostic signal that could be detected remotely. But you can also imagine and were working on circuits that give off chemotherapy that would kill the tumor directly. And making smart circuits do that in response of ways. And you can even imagine having mixtures of bacteria that do both diagnosis and therapy. So I think there's really a whole world of possibilities once you start thinking about using bacteria as a platform upon which to engineer functions.”

巴蒂亚：“最让我们兴奋的是你可以让合成生物学的技术与诊断学与治疗学融合。在这个例子中，我们使微生物生成了可以远程探测的信号。你也完全可以想像让微生物直接释放可以杀死肿瘤的化学物质。你甚至还可以想像利用混合微生物同时进行诊断与治疗。一旦你开始思考如何利用微生物这一平台实现你的目标，你会发现，你面前将是一个充满无限可能的新世界。”