機械化實驗室·基因機器

最新 04-05

大家好，我是M君，一個集經驗

與才華於一身的良心小編。

你聽說過DNA鑄造廠嗎？你知道「基因零件庫」嗎？今天這篇雙語閱讀，和M君一起，走入現代科學的世界吧！

Robot laboratories

機械化實驗室

Gene machines

基因機器

The design of synthetic lifeforms could become a new industry.

合成生命體設計可能成為一個新產業。

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.

倫敦DNA鑄造廠（London DNA Foundry）座落在帝國理工學院的地下室里。「鑄造廠」一詞會讓人想起液態金屬被倒入模具的場面，也就是工業革命早期的場景。然而，這座鑄造廠絕對是現代的產物。那裡的確有液體被四處移動和灌注，但量極少，而且也不是金屬，而是包含生命遺傳密碼的懸濁液。

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.

一場廣泛的運動正在發生，這個實驗室只是其中一例。從馬薩諸塞州劍橋市的布羅德研究所（Broad Institute）到矽谷，再到新加坡國立大學，類似的生物鑄造廠正在全球各地建立起來。它們都能集中完成基因工程研究中那些乏味而又繁重的工作。生物技術公司無須再購入和運營自己的實驗室，生物鑄造廠將為之代勞。

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.

倫敦DNA鑄造廠的操作室裡布滿了盒子狀的設備，每台設備都可以反覆而快速地完成一項特定的操作，例如移液。一條機械臂在機器之間傳送小型塑料測試皿。每個測試皿內最多有1536個微孔，每個微孔內注有數微升的液體和多條DNA鏈。通過這種方式，該鑄造廠可精確按所需濃度在一個早上配製15萬個DNA樣本。

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.

這個過程的起點是一個庫，存有該鑄造廠自動化主管大衛·麥克利蒙（David McClymont）所說的「零件」。所謂零件其實是一些遺傳密碼片段，可用於組裝不同的遺傳「迴路」。在生物技術術語中，一個迴路就是協作完成一個共同目標的一組基因，比如協作生成一系列酶來把某種化學物質轉化為另一種化學物質。接下來，鑄造廠會把有可能構成一組迴路的基因組裝成名為「質粒」的環狀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.

要得到合適的質粒，鑄造廠的客戶可直接從「基因零件庫」里訂購，也可以提供自己專有的遺傳密碼片段。一切所需零件隨後會被轉移到測試皿中帶條形碼的微孔內，然後這些物質會自動混合。整個過程由客戶提供的、描述該實驗的計算機代碼控制。

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後，測試板將被放入一台機器中，通過名為聚合酶鏈式反應（PCR）的過程令每個微孔中的質粒繁殖。完成PCR後，形成的質粒會被導入活細胞——細菌或酵母。之後，鑄造廠會培養這些細胞，並測試結果，確定是否有能按預期發揮作用的迴路。

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.

倫敦DNA鑄造廠每天可生成並測試約15,000個不同的基因迴路設計。誠如其名，該鑄造廠僅生產和測試DNA質粒。而其他一些生物鑄造廠則提供更廣泛的服務，例如矽谷公司Transcriptic還讓客戶存儲整個細胞系供日後測試，或者從這些細胞系中培養組織來做測試。

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的一大專長是臨床前藥物篩選。這涉及測試大量最終可能成為藥物的化合物。例如，如果要找一種藥物來改變某種在細胞內外運輸鈣的蛋白質的運作，那麼既要用懸浮液里的這種蛋白質來篩選潛在藥物，也要細胞膜中帶有這類通道的完整細胞來測試。

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的許多客戶都是新創立而無力購買自有測試設施的小公司。其中一家是同樣位於矽谷的Pliant Therapeutics，該公司正利用Transcriptic的服務來測試針對纖維化疾病（在肺部和心臟等器官形成疤痕組織）的療法。不過也有大型老公司使用Transcriptic的設施，這往往要比在公司內部做測試更省錢。

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.

這個行業才剛剛起步，目前各家生物鑄造廠仍各行其是。但倫敦DNA鑄造廠的董事保羅·弗里蒙特（Paul Freemont）希望，在明確了客戶對哪些流程最感興趣後，其他領域常見的那類行業標準也會在生物鑄造廠中出現。這會為設計新合成生命體這項工作提供助力，使之從如今的小型定製業務變成更為全球性的產業。這一天還沒到來。但只要有需求，生物鑄造廠勢必會在工業革命的下一階段發揮作用。