Robot Laboratories: Gene Machines

机械化实验室：基因机器

 

The design of synthetic lifeforms could become a new industry

合成生命体设计可能成为一个新产业

 

In the basement of Imperial College sits the London DNA Foundry. The word “foundry” calls forth images of liquid metal being poured into moulds – of the early phase of the Industrial Revolution, in other words. This foundry is, however, determinedly modern. Liquid is indeed being moved around and poured. But it is in minuscule quantities, and it is not metal. Instead, it is an aqueous suspension of the genetic codes of life.

 

伦敦DNA铸造厂（London DNA Foundry）座落在帝国理工学院的地下室里。“铸造厂”一词会让人想起液态金属被倒入模具的场面，也就是工业革命早期的场景。然而，这座铸造厂绝对是现代的产物。那里的确有液体被四处移动和灌注，但量极少，而且也不是金属，而是包含生命遗传密码的悬浊液。

 

The laboratory is an example of a wider movement. Similar biofoundries are being set up around the world, from the Broad Institute in Cambridge, Massachusetts, via Silicon Valley, to the National University of Singapore. All offer ways of centralising the donkey work of genetic-engineering research. Instead of biotechnology companies buying and operating their own laboratories, foundries will do it for them.

 

一场广泛的运动正在发生，这个实验室只是其中一例。从马萨诸塞州剑桥市的布罗德研究所（Broad Institute）到硅谷，再到新加坡国立大学，类似的生物铸造厂正在全球各地建立起来。它们都能集中完成基因工程研究中那些乏味而又繁重的工作。生物技术公司无须再购入和运营自己的实验室，生物铸造厂将为之代劳。

 

London DNA Foundry’s operations room is filled with boxy devices, each designed to do one particular operation, such as pipetting, repeatedly and quickly. A robotic arm shuttles small plastic dishes between the machines. Each dish contains up to 1,536 minuscule wells. And in each of those wells sits several microlitres of liquid and a few strands of DNA. Using this arrangement, the foundry can mix, in the precise concentrations required, 150,000 samples of DNA in a morning.

 

伦敦DNA铸造厂的操作室里布满了盒子状的设备，每台设备都可以反复而快速地完成一项特定的操作，例如移液。一条机械臂在机器之间传送小型塑料测试皿。每个测试皿内最多有1536个微孔，每个微孔内注有数微升的液体和多条DNA链。通过这种方式，该铸造厂可精确按所需浓度在一个早上配制15万个DNA样本。

 

The starting-point for the process is a library of what David McClymont, the foundry’s head of automation, calls “parts”. These are snippets of genetic code from which different genetic “circuits” can be assembled. A circuit, in biotech speak, is a collection of genes that work together towards a common goal – for example, generating a series of enzymes that convert one type of chemical into another. The genes comprising a potential circuit are then assembled into circular DNA molecules called plasmids.

 

这个过程的起点是一个库，存有该铸造厂自动化主管大卫·麦克利蒙（David McClymont）所说的“零件”。所谓零件其实是一些遗传密码片段，可用于组装不同的遗传“回路”。在生物技术术语中，一个回路就是协作完成一个共同目标的一组基因，比如协作生成一系列酶来把某种化学物质转化为另一种化学物质。接下来，铸造厂会把有可能构成一组回路的基因组装成名为“质粒”的环状DNA分子。

 

To obtain appropriate plasmids the foundry’s customers may simply order parts from the library. They may also provide their own proprietary snippets. All the required parts are then transferred to bar-coded wells in the dishes and their contents mixed automatically. The whole process is controlled by a piece of computer code, provided by the customer, that describes the experiment.

 

要得到合适的质粒，铸造厂的客户可直接从“基因零件库”里订购，也可以提供自己专有的遗传密码片段。一切所需零件随后会被转移到测试皿中带条形码的微孔内，然后这些物质会自动混合。整个过程由客户提供的、描述该实验的计算机代码控制。

 

Once the mixture is correct, the test plates are whisked into a machine which multiplies the number of plasmids in each well using a process called a polymerase chain reaction (PCR). And then, when the PCR has done its work, the plasmids are introduced into living cells – either bacterial or yeast. After that, the cells are incubated, and the result is tested to see which, if any, of the circuits performs as expected.

 

得到了合乎要求的混合物后，测试板将被放入一台机器中，通过名为聚合酶链式反应（PCR）的过程令每个微孔中的质粒繁殖。完成PCR后，形成的质粒会被导入活细胞——细菌或酵母。之后，铸造厂会培养这些细胞，并测试结果，确定是否有能按预期发挥作用的回路。

 

Such is the London DNA Foundry’s scale that it can build and test about 15,000 different genetic designs in a day. True to its name, the foundry is set up to build and test DNA plasmids only. Some other biofoundries, however, offer a wider range of services. For example Transcriptic, a firm in Silicon Valley, will also allow customers to store entire cell lines that may be tested later, or to grow tissues from them for testing.

 

伦敦DNA铸造厂每天可生成并测试约15,000个不同的基因回路设计。诚如其名，该铸造厂仅生产和测试DNA质粒。而其他一些生物铸造厂则提供更广泛的服务，例如硅谷公司Transcriptic还让客户存储整个细胞系供日后测试，或者从这些细胞系中培养组织来做测试。

 

One of Transcriptic’s particular specialities is preclinical drug screening. This involves testing vast numbers of compounds that might possibly end up as drugs. A drug might, for example, be intended to alter the operation of a particular protein that shuttles, say, calcium in and out of a cell. In that case, potential drugs might be screened against both the protein in free suspension, and intact cells that have such channels in their membranes.

 

Transcriptic的一大专长是临床前药物筛选。这涉及测试大量最终可能成为药物的化合物。例如，如果要找一种药物来改变某种在细胞内外运输钙的蛋白质的运作，那么既要用悬浮液里的这种蛋白质来筛选潜在药物，也要细胞膜中带有这类通道的完整细胞来测试。

 

Many of Transcriptic’s customers are small, newly founded firms that cannot afford their own test facilities. One such, Pliant Therapeutics, also in Silicon Valley, is using Transcriptic to test treatments for fibrotic disease – the formation of scar tissue in places like the lungs and the heart. Large, established firms use its facilities, too, though. It is often cheaper for them to do so than to carry out tests in house.

 

Transcriptic的许多客户都是新创立而无力购买自有测试设施的小公司。其中一家是同样位于硅谷的Pliant Therapeutics，该公司正利用Transcriptic的服务来测试针对纤维化疾病（在肺部和心脏等器官形成疤痕组织）的疗法。不过也有大型老公司使用Transcriptic的设施，这往往要比在公司内部做测试更省钱。

 

At the moment, each foundry is going its own way, as the industry finds its feet. But Paul Freemont, a director of the London DNA Foundry, hopes that once it is clear what processes are of most interest to customers, the sorts of industrial standards which are commonplace in other industries will start to emerge among biofoundries. That will make it easier for the process of designing new synthetic lifeforms to be scaled up from the bespoke boutique business it is now to something more like a global industry. That day is not yet here. But if there is demand, then biofoundries will surely play their part in the next phase of the Industrial Revolution.

 

这个行业才刚刚起步，目前各家生物铸造厂仍各行其是。但伦敦DNA铸造厂的董事保罗·弗里蒙特（Paul Freemont）希望，在明确了客户对哪些流程最感兴趣后，其他领域常见的那类行业标准也会在生物铸造厂中出现。这会为设计新合成生命体这项工作提供助力，使之从如今的小型定制业务变成更为全球性的产业。这一天还没到来。但只要有需求，生物铸造厂势必会在工业革命的下一阶段发挥作用。

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