Computation Comes to Life

For years biologists have used computer models and high-performance computers to simulate and understand living processes. More recently, computer scientists have drawn inspiration from biology to immunize information systems against malware and to create algorithms that mutate without human intervention. In all such cases, the underlying computer architecture has remained traditional and unremarkable——software running on silicon-based digital processors.

But now researchers are taking the marriage of computer science and biology to a remarkable new level, turning cells into living computers with programmable DNA and biochemical memories, sensors, actuators and intercellular communication mechanisms.

Chip-making processes today place atoms of silicon and dopants——impurities added to define the chip's electrical properties——crudely but well enough to make the chips work. As circuits shrink, however, it's getting harder to put the atoms, particularly the dopant atoms, in exactly the right places.

But biological processes for millions of years have been able to place single molecules and atoms in precisely the right order and locations.

Rather than wait centuries for conventional engineering to catch up, Thomas Knight, an MIT researcher and a pioneer in the field and researchers at a handful of universities want to ride on the back of biology or, more precisely, inside the cell. Knight and a group of graduate students are building a tool kit of what they call BioBricks, standard parts that can be used to build programmable organisms.

Each of some 400 BioBricks is housed in a little vial of liquid containing copies of a carefully chosen and well-understood section of DNA. Each DNA fragment can mimic in some way the operations of conventional computer circuits. BioBricks can be used individually to perform very simple tasks, or they can be spliced together to do higher-level work. They allow someone to build programmable organisms without understanding the underlying biology.

There are BioBricks that act as logic gates, performing simple Boolean operations such as AND, NOT, NOT AND, OR, NOT OR and so on. For example, the AND BioBrick generates an output signal when it gets a biochemical signal from both its inputs, whereas an OR BioBrick produces a signal if it gets a signal from either input.

These biological components work extremely slowly by the standards of conventional computers, performing their functions in seconds or minutes rather than nanoseconds, and Knight says they are unlikely ever to exceed millisecond-level performance. But that doesn't mean you couldn't use biological components to produce, say, carbon nanotubes, that in turn could be used to build molecular-scale high-performance computers.

Or, Knight says, it's possible that living factories made from BioBricks could help build ultradense silicon chips by replacing the troublesome dopant atoms at just the right points on a silicon lattice.

Ron Weiss, a former student of Knight's and now a professor of electrical engineering and molecular biology at Princeton University, is working on digital logic inside cells and intercellular communications. He says it will be a long time before synthetic biology contributes directly to computer science. “But eventually we might come up with an abstraction that allows you to program billions of little biological computing elements that are not robust at all and don't have a lot of resources,”Weiss says, “and that might be a useful paradigm for programming certain kinds of silicon-based computational devices.”

Scientists at the University of Alberta in Edmonton are trying to develop a plant whose leaf shape or flower color changes when a land mine is buried below it. Roots would have to be genetically altered to detect explosives traces in the soil and to communicate that information to the leaves or flowers.

That will require some kind of sensor circuits in the plants' root cells, plus an actuator circuit in the leaf or flower cells, with little real computation in between. But, Knight says, one can imagine more-sophisticated computational engines inside a plant's cell that would, for example, cause the plant to bloom on Mother's Day or prepare itself for frost or drought based on warnings input by human weather forecasters.

But he's clearly uncomfortable speculating about miraculous applications of synthetic biology. A great deal of effort must first go into developing the kinds of design and measurement tools and methods that conventional engineers take for granted.

The ability of biological circuits to self-replicate makes synthetic biology unique among all engineering disciplines, Knight says. “Tremendous power comes from that, and some dangers,” he says.

Researchers at MIT are limiting their work to two kinds of agents. The first are natural agents that are 100% safe, and the second are engineered organisms “not known to consistently cause disease in healthy adult humans,”the government's definition of Biosafety Level 1 on its four-level scale of infection dangers. And, Knight adds, his work involves simplifying organisms, not adding features that could make them dangerous.

The greater danger in synthetic biology, Knight says, comes from the possibility that others will exploit it for evil purposes. “All powerful technologies are dangerous, and we are creating a powerful technology,”he says. “Our best defense is our ability to do it faster, better and cheaper than anyone else.”

計算進入生命科學(xué)

多年來，生物學(xué)家利用計算機模型和高性能計算機模擬和了解生命過程。最近，計算機科學(xué)家從生物學(xué)獲得靈感，(開發(fā)出)使信息系統(tǒng)對惡意軟件免疫(的技術(shù))，還編制出無需人工干預(yù)就能變異的算法。在這些情況下，基礎(chǔ)的計算機架構(gòu)仍是傳統(tǒng)的和常態(tài)的——軟件運行在基于硅的數(shù)字處理器上。

但現(xiàn)在，研究人員在一個全新的層面上將計算機科學(xué)與生物學(xué)聯(lián)姻，把細(xì)胞變成擁有可編程DNA與生化存儲器、傳感器、激勵器和細(xì)胞間通信機制的有生命的計算機。

今天的芯片制造工藝是將硅和摻雜物(加入的雜質(zhì)決定芯片的電氣特性)的原子進行排列，原始但足以使芯片工作。然而，隨著電路縮小，將原子、尤其是摻雜物的原子放到正確的地方越來越難。

但是，經(jīng)過幾百萬年(進化的)生物過程能以非常精確的序列和位置放置單個分子和原子。

此領(lǐng)域的先驅(qū)、MIT的研究人員Thomas Knight，以及一些大學(xué)的研究者不想再等上幾個世紀(jì)讓常規(guī)的工程技術(shù)趕上來，他們要駕馭生物學(xué)，更準(zhǔn)確地講，進入細(xì)胞內(nèi)。Knight和一群研究生正在開發(fā)稱之為BioBricks的工具套件，它們是能用來制造可編程有機體的標(biāo)準(zhǔn)部件。

他們將大約400個BioBricks裝在一只裝有液體的小瓶里，里面包含著一個經(jīng)仔細(xì)選擇并完全了解的DNA片段的復(fù)制品。每個DNA片段能以某種方式模擬常規(guī)計算機電路的操作。每個BioBricks能用于執(zhí)行非常簡單的任務(wù)，或者能合在一起完成更高級的工作。它們也能讓不懂基礎(chǔ)生物學(xué)的人生成可編程的有機體。

有的BioBrick能起邏輯門的作用，能完成簡單的布爾運算，如與、非、與非、或、 或非等等。例如，BioBrick中有兩個輸入都收到生化信號時就產(chǎn)生“與”信號輸出，而BioBrick在其中任何一個輸入上得到信號就產(chǎn)生“或”信號輸出。

按常規(guī)計算機的標(biāo)準(zhǔn)，這些生物部件工作得非常慢，以秒或者分而不是以納秒完成其功能，Knight認(rèn)為，它們不可能超過毫秒級的性能。但這并不意味你不能用生化部件生成碳納管，隨后再用碳納管制造分子級的高性能計算機。

或者，如Knight所說，用BioBrick構(gòu)成生命工廠是有可能的，它通過替代硅晶格適當(dāng)位置上令人討厭的摻雜原子幫助制造集成度極高的硅芯片。

Ron Weiss是Knight過去的學(xué)生，現(xiàn)在是普林斯頓大學(xué)電氣工程系的教授，他正在研究細(xì)胞內(nèi)的數(shù)字邏輯和細(xì)胞間的通信。他認(rèn)為，合成生物學(xué)能對計算機科學(xué)直接做出貢獻還需要很長的時間。他說：“最終我們可能會形成這樣一個概念，允許對數(shù)以億計的小小的生物計算單元進行編程，雖然這些單元從整體上講不是強健的、也不具有很多資源，但對某些基于硅的計算部件而言這可能是一種有用的編程范例?！?/P>

(加拿大)愛德蒙頓市的阿爾伯達(dá)大學(xué)的科學(xué)<