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我要向大家展示的是創造身體活組織的神奇分子機器。分子非常、非常小。說到小呢,我的意思是真的很小,它們比光的波長還小,所以我們無法直接觀察它們。但藉由科學,我們對分子的大小已瞭解得相當透徹,所以我們能夠談論關於分子的種種,但沒有直接展示分子模樣的方法。
有一種方法是畫圖。事實上這並非新方法,科學家們總是創造圖片,作為他們思考和發現過程的一部分。他們藉由眼睛、望遠鏡和顯微鏡之類的科技工具觀察,並用大腦思考而繪製出這些圖像。我舉兩個眾所周知的例子,他們以藝術來表達科學而聞名。
我先從伽利略開始。伽利略用世上第一台望遠鏡來觀察月亮,他改變了我們對月亮的認知。17世紀時,人們認為月亮是完美的天體,但伽利略見到的是一個佈滿岩石的不毛之地,他藉由水彩畫表達出這幅景象。
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以下為系統擷取之英文原文
What I'm going to show you are the astonishing molecular machines that create the living fabric of your body. Now molecules are really, really tiny. And by tiny, I mean really. They're smaller than a wavelength of light, so we have no way to directly observe them. But through science, we do have a fairly good idea of what's going on down at the molecular scale. So what we can do is actually tell you about the molecules, but we don't really have a direct way of showing you the molecules.
One way around this is to draw pictures. And this idea is actually nothing new. Scientists have always created pictures as part of their thinking and discovery process. They draw pictures of what they're observing with their eyes, through technology like telescopes and microscopes, and also what they're thinking about in their minds. I picked two well-known examples, because they're very well-known for expressing science through art.
And I start with Galileo who used the world's first telescope to look at the Moon. And he transformed our understanding of the Moon. The perception in the 17th century was the Moon was a perfect heavenly sphere. But what Galileo saw was a rocky, barren world,which he expressed through his watercolor painting.
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另一位科學家有個遠大的想法,這位生物界的超級巨星就是查爾斯.達爾文。他的筆記裡有句著名的開場白,他從左上角開始寫道:「我認為。」然後畫出第一棵生命樹,這就是他對地球上所有物種及生物如何藉由進化歷史而連接起來的見解。物種起源來自於物兢天擇,從遠古的生物族群開始分支。
即使身為一名科學家,參加過分子生物學家的演講,我發現自己完全無法理解他們描述研究的那些艱澀術語與行話,直到我看見David Goodsell的藝術作品。他是Scripps研究所的分子生物學家,他所繪的圖,每個部份都相當精確,依照實物比例,他的作品讓我瞭解我們體內的分子世界是什麼模樣。
所以這是血管內血液的截面圖,你可以看到左上角這個黃綠色區域,它代表血流部份,大多是水分,但也有抗體、糖分和荷爾蒙之類的東西。紅色區域是紅血球切片,紅色分子代表血紅蛋白。它們確實是紅色,也就是血液的顏色。血紅蛋白就像一個分子海綿,在肺裡吸收氧氣,再帶到身體其他部位。
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Another scientist with very big ideas, the superstar of biology, is Charles Darwin. And with this famous entry in his notebook, he begins in the top left-hand corner with, "I think," and then sketches out the first tree of life, which is his perception of how all the species, all living things on Earth, are connected through evolutionary history -- the origin of species through natural selection and divergence from an ancestral population.
Even as a scientist, I used to go to lectures by molecular biologists and find them completely incomprehensible, with all the fancy technical language and jargon that they would use in describing their work, until I encountered the artworks of David Goodsell,who is a molecular biologist at the Scripps Institute. And his pictures, everything's accurate and it's all to scale. And his work illuminated for me what the molecular world inside us is like.
So this is a transection through blood. In the top left-hand corner, you've got this yellow-green area. The yellow-green area is the fluids of blood, which is mostly water, but it's also antibodies, sugars, hormones, that kind of thing. And the red region is a slice into a red blood cell. And those red molecules are hemoglobin. They are actually red; that's what gives blood its color. And hemoglobin acts as a molecular sponge to soak up the oxygen in your lungs and then carry it to other parts of the body.
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很多年前,我受到這個圖像啟發,思考是否能用電腦繪圖來描繪分子世界;它會是什麼模樣?這就是我開始這項工作的原因,我們來看一下吧!
這是典型的DNA雙螺旋結構,來自X光晶體繞射,所以這是精確的DNA模型。如果我們將雙螺旋展開,把兩股拉開,你們可以看到它就像牙齒一樣。這些是遺傳密碼字母,代表DNA上25000個基因,這就是人們通常談論的-這就是人們所說的遺傳密碼,但我想從不同角度來談論DNA科學,那就是DNA的物理性質。這兩股線朝不同方向延伸,我現在沒時間詳述其中原因,但它們確實朝不同方向延伸,這為人體活細胞增添許多複雜性,你們將會看到,尤其是在DNA複製過程中。
我即將給你們看的是一個精確的描述,關於DNA在人體內的實際複製機制,至少以2002年所知的生物學來說。所以DNA從左邊進入生產線,撞上這一堆小型生化機器,它們將DNA鏈拉開,進行複製,所以DNA進入這個藍色、甜甜圈狀的結構,被分成兩股,其中一股可以直接複製,你可以看到這些DNA鏈從底部旋繞而出,但另一股就沒這麼簡單,因為它必須反向複製,所以它反覆地從這些圈狀物中釋出,一次複製一段,創造兩個新DNA分子。
此刻有數十億個這樣的機器正在你體內運作,精確地複製著你的DNA。這是個精確的描述,它的速度跟你體內所進行的一樣,但我省略了誤差校正和其他部份,這是幾年前的作品,謝謝。
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I was very much inspired by this image many years ago, and I wondered whether we could use computer graphics to represent the molecular world. What would it look like?And that's how I really began. So let's begin.
This is DNA in its classic double helix form. And it's from X-ray crystallography, so it's an accurate model of DNA. If we unwind the double helix and unzip the two strands, you see these things that look like teeth. Those are the letters of genetic code, the 25,000 genes you've got written in your DNA. This is what they typically talk about -- the genetic code -- this is what they're talking about. But I want to talk about a different aspect of DNA science,and that is the physical nature of DNA. It's these two strands that run in opposite directions for reasons I can't go into right now. But they physically run in opposite directions, which creates a number of complications for your living cells, as you're about to see, most particularly when DNA is being copied.
And so what I'm about to show you is an accurate representation of the actual DNA replication machine that's occurring right now inside your body, at least 2002 biology. So DNA's entering the production line from the left-hand side, and it hits this collection, these miniature biochemical machines, that are pulling apart the DNA strand and making an exact copy. So DNA comes in and hits this blue, doughnut-shaped structure and it's ripped apart into its two strands. One strand can be copied directly, and you can see these things spooling off to the bottom there. But things aren't so simple for the other strand because it must be copied backwards. So it's thrown out repeatedly in these loopsand copied one section at a time, creating two new DNA molecules.
Now you have billions of this machine right now working away inside you, copying your DNA with exquisite fidelity. It's an accurate representation, and it's pretty much at the correct speed for what is occurring inside you. I've left out error correction and a bunch of other things. This was work from a number of years ago. Thank you.
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這是幾年前的作品。接下來我要給你們看的是最新的科學、最新的技術。同樣地,我們從DNA開始。因為被分子包圍,它會不停地擺動,我已將分子移除,方便你們觀察DNA的截面。大約是兩奈米,確實非常小,但在你的每一個細胞裡,每股DNA的長度大約是3至4千萬奈米。為了讓DNA有組織及規律地取得遺傳密碼,它被這些紫色蛋白質包裹-就是我以紫色標示的部份。它被妥善包裹,這裡所看到的都是單股DNA,這一大群纏繞在一起的DNA被稱為染色體,我們稍後再回頭來談染色體。
我們將鏡頭往外拉,拉到核孔外。核孔是通往DNA儲存處,即細胞核的通道。這裡所看到的影片相當於一學期生物課內容,我將它壓縮成7分鐘,所以我們今天是否能講那麼詳細?不行,我被告知,「不行。」
這是在光學顯微鏡下看到的活細胞,採用慢速攝影,所以你們能看到它在動。核膜打開了,這些香腸形物體是染色體,我們將目標放在這裡。它們以這些小紅點為中心,進行非常明顯的運動,當細胞準備好時會鬆開染色體,一組DNA前往一側,另一組DNA前往另一側,這是完全複製的DNA;接著細胞在中間分裂。同樣地,此刻你體內正有數十億的細胞進行這個過程。
我們回頭來看染色體,觀察它的結構,做些解說。所以,同樣地,現在染色體移到赤道板上(紡錘體腰部的橫截面),染色體排成一列。如果我們分離一條染色體,將它拉出,觀察結構,這是體內最大的分子結構之一,至少以目前的發現來說。這是一條單股染色體,每條染色體有兩股DNA,一條被捲進這條香腸形結構中,另一條被捲進另一條香腸形結構中。
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This is work from a number of years ago, but what I'll show you next is updated science, it's updated technology. So again, we begin with DNA. And it's jiggling and wiggling there because of the surrounding soup of molecules, which I've stripped away so you can see something. DNA is about two nanometers across, which is really quite tiny. But in each one of your cells, each strand of DNA is about 30 to 40 million nanometers long. So to keep the DNA organized and regulate access to the genetic code, it's wrapped around these purple proteins -- or I've labeled them purple here. It's packaged up and bundled up. All this field of view is a single strand of DNA. This huge package of DNA is called a chromosome. And we'll come back to chromosomes in a minute.
We're pulling out, we're zooming out, out through a nuclear pore, which is the gateway to this compartment that holds all the DNA called the nucleus. All of this field of view is about a semester's worth of biology, and I've got seven minutes. So we're not going to be able to do that today? No, I'm being told, "No."
This is the way a living cell looks down a light microscope. And it's been filmed under time-lapse, which is why you can see it moving. The nuclear envelope breaks down.These sausage-shaped things are the chromosomes, and we'll focus on them. They go through this very striking motion that is focused on these little red spots. When the cell feels it's ready to go, it rips apart the chromosome. One set of DNA goes to one side, the other side gets the other set of DNA -- identical copies of DNA. And then the cell splits down the middle. And again, you have billions of cells undergoing this process right now inside of you.
Now we're going to rewind and just focus on the chromosomes and look at its structure and describe it. So again, here we are at that equator moment. The chromosomes line up. And if we isolate just one chromosome, we're going to pull it out and have a look at its structure. So this is one of the biggest molecular structures that you have, at least as far as we've discovered so far inside of us. So this is a single chromosome. And you have two strands of DNA in each chromosome. One is bundled up into one sausage. The other strand is bundled up into the other sausage.
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這些從另一頭伸出、像鬍鬚的東西是細胞的動態支架,它們被稱為微管。名稱不重要,我們的目標是這個紅色區域,我將它標示為紅色,這是介於動態支架和染色體之間的介面,顯然它是染色體運作中樞,我們並不清楚它的運作原理。
我們已花了一百多年時間致力於研究這個叫著絲點的東西,我們的研究仍處於初期階段。它大約由200種不同的蛋白質組成,其中共有上千種蛋白質;它是一個訊號傳播系統,藉由化學訊號傳播,當它覺得一切準備就緒,可進行染色體分裂時,就告訴其他細胞它準備好了。它可連接到正在形成及彼此縮合的微管上。
它也參與微管的形成,它能暫時與它們連接。它也是感測系統,它能感覺細胞何時準備好,染色體何時處於正確位置。這裡正變成綠色,因為它感覺到一切已準備就緒,如你們所見,這裡有一些還是紅色,它沿著微管離開,這是訊號傳播系統發出的停止訊號。它離開了,我的意思是,它具有機械性質,這是分子的機械性質。
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These things that look like whiskers that are sticking out from either side are the dynamic scaffolding of the cell. They're called mircrotubules. That name's not important. But what we're going to focus on is this red region -- I've labeled it red here -- and it's the interfacebetween the dynamic scaffolding and the chromosomes. It is obviously central to the movement of the chromosomes. We have no idea really as to how it's achieving that movement.
We've been studying this thing they call the kinetochore for over a hundred years with intense study, and we're still just beginning to discover what it's all about. It is made up of about 200 different types of proteins, thousands of proteins in total. It is a signal broadcasting system. It broadcasts through chemical signals telling the rest of the cell when it's ready, when it feels that everything is aligned and ready to go for the separation of the chromosomes. It is able to couple onto the growing and shrinking microtubules.
It's involved with the growing of the microtubules, and it's able to transiently couple onto them. It's also an attention sensing system. It's able to feel when the cell is ready, when the chromosome is correctly positioned. It's turning green here because it feels that everything is just right. And you'll see, there's this one little last bit that's still remaining red. And it's walked away down the microtubules. That is the signal broadcasting system sending out the stop signal. And it's walked away. I mean, it's that mechanical. It's molecular clockwork.
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這就是分子層面上的運作情形。所以稍微美化一下這些分子,我們畫出了驅動蛋白,以橘色表示。它們是分子的信差,朝單一方向前進。這是動力蛋白,它們攜帶這個傳播系統,它們有長長的腿,能跨越障礙物等等。所以,同樣地,以科學角度來說,這一切表達都很精確,問題是我們無法以別的方法向大眾展示。
以人類的領悟力前沿來探索尖端科學相當令人興奮,探索這些東西確實是科學研究中令人愉快的動力,但大多數醫學研究者們-探索這些東西只是通往遠大目標過程中的步驟,那就是根除疾病,減少疾病造成的痛苦和不幸,彌補人類的不足之處。
謝謝。
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This is how you work at the molecular scale. So with a little bit of molecular eye candy,we've got kinesins, which are the orange ones. They're little molecular courier molecules walking one way. And here are the dynein. They're carrying that broadcasting system. And they've got their long legs so they can step around obstacles and so on. So again, this is all derived accurately from the science. The problem is we can't show it to you any other way.
Exploring at the frontier of science, at the frontier of human understanding, is mind-blowing. Discovering this stuff is certainly a pleasurable incentive to work in science. But most medical researchers -- discovering the stuff is simply steps along the path to the big goals, which are to eradicate disease, to eliminate the suffering and the misery that disease causes and to lift people out of poverty.
Thank you.