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在接下來15分鐘左右的時間裡,我想做的是試著告訴大家一些關於如何賦予物質生命的想法。這似乎有點好高騖遠;但當你看看自己,看看你的手,你意識到自己是活生生的。因此,這是一個開始。生命的追尋開始於四十億年的地球,有機、生物性的生命已存在了40億年。身為無機化學家的我,我的朋友和同事在有機、有生命的世界和無機、無生命的世界之間畫出了區分的界線。我打算嘗試進行的是,提出一些想法,關於如何將無機、無生命的物質轉變成有生命的物質,轉變成無機生物。
在這麼做之前,我想稍微敘述一下關於生物學的事。我對生物學相當著迷,我喜歡研究合成生物學,我喜歡活生生的東西,我喜歡研究生物學的基本架構。但在這個基本架構當中,我們必須記住,生物學的驅動力事實上來自於演化。雖然演化這個理論是100多年前由達爾文及許多其他科學家建立的,但演化論還是有些令人難解之處。當我提到達爾文的演化論時,我指的是一個論點,就只有一個論點,那就是適者生存。所以先別以形而上學的方式來思考演化論,只要以後代、競爭及競爭優勝者的角度來思考演化論。
因此,思及這一點,身為化學家的我,想自問一個關於生物學中未提及的問題:適用於達爾文演化論的最小物質單位為何?這似乎是個相當深刻的問題,身為一位化學家,我們不習慣每天思考深刻的問題。所以,當我思考這個問題時,突然意識到,生物學能給我們答案。事實上,能獨立演化的最小物質單位就是單細胞-即細菌。
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以下為系統擷取之英文原文
What I'm going to try and do in the next 15 minutes or so is tell you about an idea of how we're going to make matter come alive. Now this may seem a bit ambitious, but when you look at yourself, you look at your hands, you realize that you're alive. So this is a start. Now this quest started four billion years ago on planet Earth. There's been four billion years of organic, biological life. And as an inorganic chemist, my friends and colleagues make this distinction between the organic, living world and the inorganic, dead world. And what I'm going to try and do is plant some ideas about how we can transform inorganic, dead matter into living matter, into inorganic biology.
So before we do that, I want to kind of put biology in its place. And I'm absolutely enthralled by biology. I love to do synthetic biology. I love things that are alive. I love manipulating the infrastructure of biology. But within that infrastructure, we have to remember that the driving force of biology is really coming from evolution. And evolution, although it was established well over 100 years ago by Charles Darwin and a vast number of other people, evolution still is a little bit intangible. And when I talk about Darwinian evolution, I mean one thing and one thing only, and that is survival of the fittest. And so forget about evolution in a kind of metaphysical way. Think about evolution in terms of offspring competing, and some winning.
So bearing that in mind, as a chemist, I wanted to ask myself the question frustrated by biology: What is the minimal unit of matter that can undergo Darwinian evolution? And this seems quite a profound question. And as a chemist, we're not used to profound questions everyday. So when I thought about it, then suddenly I realized that biology gave us the answer. And in fact, the smallest unit of matter that can evolve independently is, in fact, a single cell -- a bacteria.
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這引發了三個非常重要的問題:何謂生命?生物是特有的嗎?生物學家似乎這麼認為。物質可演化嗎?現在,如果我們以相反順序來回答這些問題,第三個問題-物質可演化嗎?如果我們能回答這個問題,我們將能夠瞭解生物的特殊性為何。或許,只是或許,我們將能對生命真正的定義有所概念。
這是一些無機生命,這是一滴無生命的晶體,我打算在它身上加工一下,它會變成活生生的。你們可以看到,它有點像在授粉、發芽、成長,這是一種無機晶體管,所有這些顯微鏡下的晶體在幾分鐘前是無生命的,但看起來卻是活生生的。當然,它們並非活著,這是一個能形成一座晶體花園的化學實驗。但當我看到這個景像時,真的很著迷,因為它看起來栩栩如生。當我將它放置幾秒鐘後,看看螢幕,你們可以看到它逐漸生長出結構,將空白處填滿。它是沒有生命的物質,所以我對這一點感到樂觀。如果我們能以某種方式讓物質模擬生命形態,那我們不妨更進一步,不妨看看是否能真正製造出生命。
但其中有個問題。因為一直到大約十年前,人們都說生命幾乎是不可能形成的,人類是宇宙中最不可思議的奇蹟。事實上,我們是宇宙中唯一的智慧生命。這讓人有點悶。所以,身為一位化學家,我想說的是,「等等,這是怎麼回事?生命真的那麼難以形成嗎?」這正是問題所在。我想,也許第一個細胞的出現很可能像行星的形成一樣。事實上,讓我們更進一步來看,比方說,如果融合的物理學蘊藏在宇宙的編碼中,也許生命的物理學也是如此。因此化學家考慮的問題-這也是個很大的優勢,我們傾向於將重點放在元素上。在生物學中,碳扮演了主要角色;在宇宙裡,只要是碳和有機生物存在之處,就存在著美妙的生命多樣性。事實上,我們擁有這些可供操控的驚人生命形式。在實驗室裡,我們非常小心地嘗試,並避免各種生物性危害。
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So this raises three really important questions: What is life? Is biology special? Biologists seem to think so. Is matter evolvable? Now if we answer those questions in reverse order, the third question -- is matter evolvable? -- if we can answer that, then we're going to know how special biology is, and maybe, just maybe, we'll have some idea of what life really is.
So here's some inorganic life. This is a dead crystal, and I'm going to do something to it, and it's going to become alive. And you can see, it's kind of pollinating, germinating, growing. This is an inorganic tube. And all these crystals here under the microscope were dead a few minutes ago, and they look alive. Of course, they're not alive. It's a chemistry experiment where I've made a crystal garden. But when I saw this, I was really fascinated, because it seemed lifelike. And as I pause for a few seconds, have a look at the screen. You can see there's architecture growing, filling the void. And this is dead. So I was positive that, if somehow we can make things mimic life, let's go one step further. Let's see if we can actually make life.
But there's a problem, because up until maybe a decade ago, we were told that life was impossible and that we were the most incredible miracle in the universe. In fact, we were the only people in the universe. Now, that's a bit boring. So as a chemist, I wanted to say, "Hold on. What is going on here? Is life that improbable?" And this is really the question. I think that perhaps the emergence of the first cells was as probable as the emergence of the stars. And in fact, let's take that one step further. Let's say that if the physics of fusion is encoded into the universe, maybe the physics of life is as well. And so the problem with chemists -- and this is a massive advantage as well -- is we like to focus on our elements. In biology, carbon takes center stage. And in a universe where carbon exists and organic biology, then we have all this wonderful diversity of life. In fact, we have such amazing lifeforms that we can manipulate. We're awfully careful in the lab to try and avoid various biohazards.
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那物質方面呢?如果我們能賦予物質生命,會發生物質性危害嗎?因此,思考一下,這是個嚴重的問題。如果筆可以複製,確實會有點問題。因此,如果我們想賦予物質生命,就必須用不同的方式思考,我們也必須謹慎看待這個問題。但在我們能製造生命之前,讓我們思考一下生命真正的特性為何。抱歉讓你們看這麼複雜的圖表,這只是細胞代謝途徑的總圖。細胞對我們來說顯然是令人著迷的東西,合成生物學家對細胞進行操作,化學家試著研究分子以瞭解疾病,你體內同時運行著這所有的代謝途徑。你的身體可進行調控、轉錄訊息、製造催化劑、產生各種機能。但細胞的功能如何運作?它會分裂、競爭、存活。我想這就是我們思考建立生命概念的起點。
但生命還有什麼特性?嗯,我喜歡將它想成一團瓶中的火焰,我們在圖中看到的是單細胞複製、代謝及藉由化學反應燃燒的過程。因此,我們必須瞭解,如果我們打算製造人造生命或瞭解生命的起源,就必須以某種方式提供動力。所以在真正著手製造生命之前,我們必須思考生命起源於何處。達爾文本人在一封寫給同事的信中寫道,他認為生命可能出現在某些溫暖的小池塘中;也許不在蘇格蘭,也許在非洲,也許在別的地方。但真正的答案是,我們對此毫無概念,因為生命的起源依然是個問號。想像一下,四十五億年前,存在一個充滿化學物質的溶液,人類從中誕生。
因此,當你思考令人意想不到的大自然時,那就是接下來幾分鐘我即將告訴你們的事,只要記住,我們來自於地球上的物質,我們經歷了各種世界,RNA研究者談論的是RNA世界;我們以某種方式成為蛋白質和DNA;然後成為最初的生命始祖;然後演化介入-這就是關鍵之處;然後人類出現。但其中有個你無法克服的障礙:你可以將基因組解碼,你可以回顧歷史,你可以藉著粒腺體DNA將所有人類的關係串聯起來,但我們無法追溯到最初的生命始祖之前,無法追溯到我們可以將其定序的最初一個可見細胞,或這個歷史之前。因此,我們無法得知人類最初的起源。
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Well what about matter? If we can make matter alive, would we have a matterhazard? So think, this is a serious question. If your pen could replicate, that would be a bit of a problem. So we have to think differently if we're going to make stuff come alive. And we also have to be aware of the issues. But before we can make life, let's think for a second what life is really characterized by. And forgive the complicated diagram. This is just a collection of pathways in the cell. And the cell is obviously for us a fascinating thing. Synthetic biologists are manipulating it. Chemists are trying to study the molecules to look at disease. And you have all these pathways going on at the same time. You have regulation; information is transcribed; catalysts are made; stuff is happening. But what does a cell do? Well it divides, it competes, it survives. And I think that is where we have to start in terms of thinking about building from our ideas in life.
But what else is life characterized by? Well, I like think of it as a flame in a bottle. and so what we have here is a description of single cells replicating, metabolizing, burning through chemistries. And so we have to understand that if we're going to make artificial life or understand the origin of life, we need to power it somehow. So before we can really start to make life, we have to really think about where it came from. And Darwin himself mused in a letter to a colleague that he thought that life probably emerged in some warm little pond somewhere -- maybe not in Scotland, maybe in Africa, maybe somewhere else. But the real honest answer is, we just don't know, because there is a problem with the origin. Imagine way back four and a half billion years ago, there is a vast chemical soup of stuff. And from this stuff we came.
So when you think about the improbable nature of what I'm going to tell you in the next few minutes, just remember, we came from stuff on planet Earth. And we went through a variety of worlds. The RNA people would talk about the RNA world. We somehow got to proteins and DNA. We then got to the last ancestor. Evolution kicked in -- and that's the cool bit. And here we are. But there's a roadblock that you can't get past. You can decode the genome, you can look back, you can link us all together by a mitochondrial DNA, but we can't get further than the last ancestor, the last visible cell that we could sequence or think back in history. So we don't know how we got here.
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因此,現在有兩種選擇:直接及間接的智慧設計-所以上帝,或我的朋友,現在來談談E.T.,把人類或一些其他的生命放在這個位置,只是進一步推論這個問題。我不是政治家,我是科學家。我們必須思考的另一件事是化學複雜性的出現,這似乎是最有可能的情形。因此,地球上出現某種原始溶液,這剛好是所有20種胺基酸的良好來源。不知怎麼的,這些胺基酸彼此結合,形成了生命。但生命的開始代表什麼意義?何謂生命?構成生命的物質為何?
因此,在1950年代,Miller及Urey做了出色的化學怪人實驗,他們製造出相當於地球早期的化學環境,他們把其中基本成分放進一個燒瓶點燃,並讓大量電流通過。他們觀察溶液中出現了什麼,發現了一些胺基酸,但其他什麼也沒有,並未產生細胞。因此,整個研究領域停擺了一段時間,直到80年代才重新開始,此時正是分析及計算機科技開始發展的時期。
在我自己的實驗室裡,我們試圖創造無機生命的方式是使用許多不同的反應形式。所以,我們試圖做的是進行反應-不是在一個燒瓶中,而是在幾十個燒瓶中,將它們連接在一起,就像流動系統一樣,全都以輸送管連接。我們可用微流體方法操作,可用光刻誘導的方式進行,也可在3D印表機上進行,我們可以讓同事在液滴中操作,關鍵在於必須有許多複雜的化學反應發生。但這可能以失敗告終,因此我們必需更加努力些。
而答案,當然就在實驗鼠身上。這讓我想起以化學家來說所需要的,我說,「嗯,我想製造分子。」但我需要新陳代謝的機制,需要一些能量;我需要一些資訊,需要一個容器;因為如果希望演化發生,就需要能彼此競爭的容器。因此,如果你有個容器,這就像坐上你的車,「這是我的車,我打算開著它繞一繞並炫耀一番。」我想像在生命形成的細胞生物學上也會有類似情形。因此,這些東西共同使演化發生,或許是這樣。在實驗室裡的測試方法就是使其最小化。
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So there are two options: intelligent design, direct and indirect -- so God, or my friend. Now talking about E.T. putting us there, or some other life, just pushes the problem further on. I'm not a politician, I'm a scientist. The other thing we need to think about is the emergence of chemical complexity. This seems most likely. So we have some kind of primordial soup. And this one happens to be a good source of all 20 amino acids. And somehow these amino acids are combined, and life begins. But life begins, what does that mean? What is life? What is this stuff of life?
So in the 1950s, Miller-Urey did their fantastic chemical Frankenstein experiment, where they did the equivalent in the chemical world. They took the basic ingredients, put them in a single jar and ignited them and put a lot of voltage through. And they had a look at what was in the soup, and they found amino acids, but nothing came out, there was no cell. So the whole area's been stuck for a while, and it got reignited in the 80s when analytical technologies and computer technologies were coming on.
In my own laboratory, the way we're trying to create inorganic life is by using many different reaction formats. So what we're trying to do is do reactions -- not in one flask, but in tens of flasks, and connect them together, as you can see with this flow system, all these pipes. We can do it microfluidically, we can do it lithographically, we can do it in a 3D printer, we can do it in droplets for colleagues. And the key thing is to have lots of complex chemistry just bubbling away. But that's probably going to end in failure, so we need to be a bit more focused.
And the answer, of course, lies with mice. This is how I remember what I need as a chemist. I say, "Well I want molecules." But I need a metabolism, I need some energy. I need some information, and I need a container. Because if I want evolution, I need containers to compete. So if you have a container, it's like getting in your car. "This is my car, and I'm going to drive around and show off my car." And I imagine you have a similar thing in cellular biology with the emergence of life. So these things together give us evolution, perhaps. And the way to test it in laboratory is to make it minimal.
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因此,我們打算做的是,想出一種無機分子的樂高積木。抱歉,螢幕上的分子看起來很複雜,但這是一些非常簡單的積木,目前或許只有三、四種不同類型的積木可用於建構。我們可以將它們組合在一起,製造出成千上萬種相當大的奈米分子,大小相當於DNA及蛋白質,但其中不含碳元素。我們不要碳元素,所以使用這些樂高積木,我們可以在沒有DNA的情況下,擁有儲存複雜訊息所需的多樣性。但我們需要製造一些容器。就在幾個月前,在我的實驗室,我們能夠以這些相當相似的分子製造細胞。你可以在螢幕上看見,一個細胞正被製造出來。我們現在打算在這個細胞裡加上一些化學物質,使其進行化學反應。我想讓你們看看,我們可以將這些分子置於細胞膜及真實細胞上,它建立了一種達爾文主義分子,一種適者生存的分子。
這部影片顯示出分子間的競爭。分子彼此競爭這些物質,它們都是由相同的物質組成,但它們希望自己的形狀取勝,它們希望自己的形狀留存下來,這就是其中關鍵。如果我們能以某種方式鼓勵這些分子彼此溝通,形成正確的形狀並彼此競爭,它們將開始形成能複製及互相競爭的細胞。如果我們能成功做到這一點,先別理會分子的細節。
讓我們回頭來看這可能意味著什麼。因此,我們擁有這個只適用於有機生物及人類的狹義演化論,如果我們能使演化進入物質世界,我建議我們該擁有一個廣義演化論,這確實值得我們思考。在宇宙中,演化控制了物質的複雜性嗎?宇宙中存在一些使物質彼此競爭的演化驅動力嗎?因此,這意味著我們可以開始發展不同的平台,探索這個演化觀點。所以想像一下,如果我們能創造一個自我形成的人造生命形式,不僅能讓我們瞭解生命的起源,很可能在宇宙中,不需要碳元素也能形成生命,可以用任何元素形成。我們可以更進一步,開發一些新技術,因為我們可以使用軟體控制,將演化過程的編碼嵌入。
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So what we're going to try and do is come up with an inorganic Lego kit of molecules. And so forgive the molecules on the screen, but these are a very simple kit. There's only maybe three or four different types of building blocks present. And we can aggregate them together and make literally thousands and thousands of really big nano-molecular molecules the same size of DNA and proteins, but there's no carbon in sight. Carbon is bad. And so with this Lego kit, we have the diversity required for complex information storage without DNA. But we need to make some containers. And just a few months ago in my lab, we were able to take these very same molecules and make cells with them. And you can see on the screen a cell being made. And we're now going to put some chemistry inside and do some chemistry in this cell. And all I wanted to show you is we can set up molecules in membranes, in real cells, and then it sets up a kind of molecular Darwinism, a molecular survival of the fittest.
And this movie here shows this competition between molecules. Molecules are competing for stuff. They're all made of the same stuff, but they want their shape to win. They want their shape to persist. And that is the key. If we can somehow encourage these molecules to talk to each other and make the right shapes and compete, they will start to form cells that will replicate and compete. If we manage to do that, forget the molecular detail.
Let's zoom out to what that could mean. So we have this special theory of evolution that applies only to organic biology, to us. If we could get evolution into the material world, then I propose we should have a general theory of evolution. And that's really worth thinking about. Does evolution control the sophistication of matter in the universe? Is there some driving force through evolution that allows matter to compete? So that means we could then start to develop different platforms for exploring this evolution. So you imagine, if we're able to create a self-sustaining artificial life form, not only will this tell us about the origin of life -- that it's possible that the universe doesn't need carbon to be alive; it can use anything -- we can then take it one step further and develop new technologies, because we can then use software control for evolution to code in.
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因此,想像我們製造一個小細胞,我們希望將它放入環境中,希望它藉由太陽獲取能量,我們所做的是,將它置於一個光照的箱中,我們不需做任何生物設計,我們瞭解其運作的力量為何,我們應該從生物中得到啟示。設計對生物來說並不重要,除非它能產生作用。因此,這將重新建構我們設計生命的方式。但不僅如此,我們將開始思考,該如何開始發展生物之間的共生關係。如果你可以將這些人造生物細胞和生物細胞融合,修正我們無法真正處理的問題,不是很棒嗎?細胞生物學真正的問題在於我們永遠無法瞭解每件事,因為這是一個由演化產生的多方面問題。演化是無法分割的,你必需以某種方式找到適合的功能。對我來說,最深刻的啟發是,如果這個想法行得通,自私基因的概念會在某個階段介入,我們就可以真正開始討論關於自私物質的概念。
在這個目前人類身為最高等生命形式的宇宙中,這意味著什麼?你們正坐在椅子上,它們並非生物,它們沒有生命;但你由物質形成,你使用物質,也掌控物質。因此,能使用這個生物及有機生物的演化觀念對我來說相當有吸引力,相當令人興奮。我們確實即將成功瞭解賦予無生命物質生命的關鍵步驟。同樣的,當你考慮到這個可能性是多麼微乎其微時,別忘了,五十億年前人類並不存在,生命亦不存在。
那麼,對於生命的起源和意義,這能告訴我們什麼?也許,對身為化學家的我來說,我不想籠統地思考這個問題,我希望能具體地思考這一點。那麼,這對定義生命來說意味著什麼?我們確實相當努力地進行這一點。我認為,如果我們能製造出無機生物,以及使物質擁有演化能力,就確實能定義何謂生命。我的目的是告訴你們,能演化的物質就有生命,這使我們有了製造可演化物質的想法。
非常感謝。
Chris Anderson:很快地問個簡短的問題。你相信這個計劃能成功嗎?什麼時候?
Lee Cronin:很多人認為生命得歷經數百萬年才能形成;只要能建立正確的化學結構,我們認為在短短幾個小時內就可完成。
CA:你認為何時會有結果?
LC:希望在未來兩年當中。
CA:這將是件了不得的大事。(笑聲)在你的想法中,其他星球上可能有非以碳為基礎的生命存在或正在形成的機率有多少?
LC:我認為有100%的機率。因為事實上我們對生物抱著相當沙文主義的想法;如果將碳除去,依然會有其他生命形成。因此,另一方面,如果我們能創造出非以碳為基礎的生命,也許我們可以告訴NASA真正該尋找的是什麼。別尋找碳元素,去尋找可演化的物質吧!
CA:Lee Cronin,祝你好運。(LC:非常感謝)
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So imagine we make a little cell. We want to put it out in the environment, and we want it to be powered by the Sun. What we do is we involve it in a box with a light on. And we don't use design anymore. We find what works. We should take our inspiration from biology. Biology doesn't care about the design unless it works. So this will reorganize the way we design things. But not only just that, we will start to think about how we can start to develop a symbiotic relationship with biology. Wouldn't it be great if you could take these artificial biological cells and fuse them with biological ones to correct problems that we couldn't really deal with? The real issue in cellular biology is we are never going to understand everything, because it's a multidimensional problem put there by evolution. Evolution cannot be cut apart. You need to somehow find the fitness function. And the profound realization for me is that, if this works, the concept of the selfish gene gets kicked up a level, and we really start talking about selfish matter.
And what does that mean in a universe where we are right now the highest form of stuff? You're sitting on chairs. They're inanimate, they're not alive. But you are made of stuff, and you are using stuff, and you enslave stuff. So using evolution in biology, and in organic biology, for me is quite appealing, quite exciting. And we're really becoming very close to understanding the key steps that makes dead stuff come alive. And again, when you're thinking about how improbable this is, remember, five billion years ago, we were not here, and there was no life. So what will that tell us
about the origin of life and the meaning of life? For perhaps, for me as a chemist, I want to keep away from general terms; I want to think about specifics. So what does it mean about defining life? We really struggle to do this. And I think, if we can make inorganic biology, and we can make matter become evolvable, that will in fact define life. I purpose to you that matter that can evolve is alive, and this gives us the idea of making evolvable matter.
Thank you very much.
(Applause)
Chris Anderson: Just a quick question on timeline. You believe you're going to be successful in this project? When?
Lee Cronin: So many people think that life took millions of years to kick in. We're proposing to do it in just a few hours, once we've set up the right chemistry.
CA: And when do you think that will happen?
LC: Hopefully within the next two years.
CA: That would be a big story. (Laughter) In your own mind, what do you believe the chances are that walking around on some other planet there is non-carbon-based life walking or oozing or something?
LC: I think it's 100 percent. Because the thing is, we are so chauvinistic to biology, if you take away carbon, there's other things that can happen. So the other thing that if we were able to create life that's not based on carbon, maybe we can tell NASA what really to look for. Don't go and look for carbon, go and look for evolvable stuff.
CA: Lee Cronin, good luck. (LC: Thank you very much.)